Effects of curcumin and ursolic acid in prostate cancer: A systematic review

Abstract

The major barriers to phytonutrients in prostate cancer therapy are non-specific mechanisms and bioavailability issues. Studies have pointed to a synergistic combination of curcumin (CURC) and ursolic acid (UA). We investigate this combination using a systematic review process to assess the most likely mechanistic pathway and human testing in prostate cancer. We used the PRISMA statement to screen titles, abstracts, and the full texts of relevant articles and performed a descriptive analysis of the literature reviewed for study inclusion and consensus of the manuscript. The most common molecular and cellular pathway from articles reporting on the pathways and effects of CURC (n = 173) in prostate cancer was NF-κB (n = 25, 14.5%). The most common molecular and cellular pathway from articles reporting on the pathways and effects of UA (n = 24) in prostate cancer was caspase 3/caspase 9 (n = 10, 41.6%). The three most common molecular and cellular pathway from articles reporting on the pathways and effects of both CURC and UA (n = 193) in prostate cancer was NF-κB (n = 28, 14.2%), Akt (n = 22, 11.2%), and androgen (n = 19, 9.6%). Therefore, we have identified the potential synergistic target pathways of curcumin and ursolic acid to involve NF-κB, Akt, androgen receptors, and apoptosis pathways. Our review highlights the limited human studies and specific effects in prostate cancer.

Keywords

Curcumin diarylheptanoid flavonoid NF-κB pentacyclic triterpenoid phytonutrients prostate cancer triterpenoid ursolic acid

Background

Prostate cancer (PCa) is the most common non-cutaneous cancer in American men. It is the second leading cause of cancer-related death in men, with 248,530 estimated new diagnoses in 2021.¹ The majority of men are diagnosed with low-risk prostate cancer, and guidelines currently emphasize close monitoring. Despite the patient anxiety associated with diagnosis, there are no drugs currently used to slow the prostate cancer progression, specifically for men on active surveillance.²

According to the 2022 AUA/ASTRO guidelines, men with clinically localized PCa as defined by clinical stage <T3 without nodal or distant metastasis on conventional imaging can be considered as candidates for active surveillance management in conjunction with individualized risk stratification including clinical T stage, serum prostate-specific antigen (PSA), Grade Group (Gleason score), and tumor volume.³ Therefore, due to the wide criteria including multiple clinical stages for men on active surveillance (up to stage T3), the large and clinically diverse patient load provides opportunity for new or additional therapy at varying stages. Active surveillance is a strategy to postpone immediate therapy with the option of delayed intervention in men with low-risk or with low volume favorable intermediate risk. Typically, the follow-up includes serial PSA blood tests, exams, and MRI imaging with repeated biopsy.⁴ The rate of clinical progression and need for treatment for patients on active surveillance is approximately 50% over 5 years, and there are limited strategies to reduce progression.⁵ Moreover, while there is no universally accepted active surveillance protocol, effective therapies, with limited side effect profiles based on scientifically justified rationales, such as phytochemicals, are urgently needed for the majority of men diagnosed with prostate cancer, due to the rate of progression and even more so for those at a higher clinical stage on active surveillance.

Dietary supplements, such as curcumin (CURC) and ursolic acid (UA), are utilized in several anti-inflammatory conditions, largely targeting NF-κB, AKT, and STAT3, common cancer molecular pathways.⁶ Investigators have suggested a variety of dietary and natural products with therapeutic benefits for prostate cancer, yet few have undergone prospective testing in humans. In a landmark study, researchers systematically discovered and proved the synergistic effect of combining the phytochemicals curcumin and ursolic acid in slowing the growth of prostate cancer.⁷ We acknowledge current clinical trials investigating CURC alone in various stages of prostate cancer (NCT03769766, NCT02724618, NCT02064673, NCT03211104); however, a synergistic approach using CURC and UA may provide a more efficacious treatment option than curcumin alone. In addition to their effects, the bioavailability of these supplements raises another issue through poor absorption, rapid metabolism, and rapid systemic elimination.^8,9 Formulations including liposomes, nanoparticles, phospholipid complexes, structural analogs and derivatives have been investigated to overcome this hurdle.

Therefore, we performed a systematic review of research studies involving prostate cancer and phytochemicals, CURC and UA, by assessing their outcomes on absorption and bioavailability and pathways and effects. Upon search, there have been no systematic reviews involving both CURC and UA in relation to prostate cancer. By investigating these phytochemicals, our hope is that the results of this review will elucidate information for others to perform future clinical trials in patients with prostate cancer, specifically those on an active surveillance regimen and/or monitoring low-grade prostate cancer.

Methods

Protocol registration

We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, which is an evidence-based minimum set of items reporting in systematic reviews.¹⁰ We registered the protocol with the International Prospective Register of Systematic Reviews (PROSPERO), registration number: 2020 CRD42020202069.

Eligibility criteria

We performed a literature review search using PubMed database encompassing all years of publications. We also gathered literature from reference lists from our relevant institutional studies and protocols without performing forward or backward citations. We excluded meta-analyses and reviews. We followed the PICO tool through the Cochrane Handbook for our inclusion criteria. For population, we included all studies with prostate cancer, in vitro and in vivo (both animal and human). For intervention we included phytonutrients curcumin and ursolic acid and any analogs. For comparison, we included placebo, or standard of care medications, or none-reported. For outcomes, we included those reporting on absorption or bioavailability and pathways or effects.

Information sources

We reviewed only published articles on PubMed database in English and performed no further communication with other study authors. Other than the previously mentioned relevant reference lists, no additional datasets were used or obtained for this review.

Search

In December 2019, we performed a comprehensive search without a set publication timeframe using the following search terms as our primary variables: “prostate cancer” and “curcumin” or “prostate cancer” and “ursolic acid.” We did not use any secondary variable search terms, such as the phytonutrients’ umbrella chemical compound classes “diarylheptanoid” or “flavonoid” for curcumin or “pentacyclic triterpenoid” or “triterpenoid.”

Study selection

We excluded all meta-analyses and reviews from the final list. We divided the literature into two broad categories: absorption or bioavailability and pathways or effects.

Data collection process

We display our data collection processes in Figures 1 and 2. One person (BDB) conducted data extraction for consistency.

Figure 1.

PRISMA flow diagram of literature search involving curcumin and prostate cancer.

Figure 2.

PRISMA flow diagram of literature search involving ursolic acid and prostate cancer.

Data items

Search terms were used in PubMed only. We did exclude studies not directly related to prostate cancer.

Risk of bias in individual studies

For human studies, we noted prospective, retrospective, or observational studies to be transparent about the strength of associations inferred from the inherent bias of study design. Additionally, for any human studies, we added the sample size of each study to provide the reader with information regarding enrollment. We did not report on publication bias.

Summary measures

We divided tables into a study outcomes group, in vitro and in vivo studies, while further dividing into animal and human studies. For both curcumin and ursolic acid separately, we also reported data on year of publication and country of origin. Furthermore, we provided summary measures for human studies involving curcumin only. Finally, we reported most common molecular and cellular pathways and bioavailability delivery methods for both CURC and UA in prostate cancer.

Synthesis of results

We performed a descriptive analysis of the literature reviewed for study inclusion and consensus of the manuscript. After initial review and selection of articles, we performed a qualitative data analysis, using the computer program NVivo (QSR International, LLC, Massachusetts, US), to find common conclusions and relationships. We did not use further statistical analysis.

Risk of bias across studies

A qualitative assessment was performed using the guidelines for assessing quality in the research based on potential biases.¹¹ We included some aspects of the confounders and outcome measurements within the summary tables.

Results

Overall search results

We located a total of 373 CURC-related studies and 41 UA-related studies in the initial search spanning from publication years 2000–2020. We present the PRISMA flow diagram for our search strategy in Figure 1 for CURC and Figure 2 for UA.

Overall, 219 studies involved CURC and PCa, while 26 studies investigated UA and PCa, with the majority focusing on molecular pathways and effects rather than absorption and bioavailability. No reviewed studies involved both CURC and UA combined. We have outlined particular groups of articles based on absorption/bioavailability, pathways/effects, in vitro, in vivo, or human (Table 1). For both phytonutrients in prostate cancer, the majority of studies were focused in vitro, 198 with CURC and 24 with UA. Alternatively, limited studies were focused in vivo, 61 with CURC and 6 with UA. Notably, there were eight (8/219, 3.7%) human studies investigating CURC effect in prostate cancer in contrast to no human studies investigating UA effect in prostate cancer. More specifically, a qualitative summary of the eight CURC-related human studies is presented in Table 2, with results focusing mainly on PSA effects.^12–19 We display the number of published articles by year in Figure 3 demonstrating a steady and increasing publication record since 2000 more so for CURC with the largest number of publications in 2017 for CURC (n = 22) and 2012 for UA (n = 5). Only two studies reported publication in 2000 since our search was initiated in late 2019. We also display the number of published articles by country of origin in Figure 4 demonstrating a majority publication record by the United States (n = 100) for CURC and China (n = 7) for UA.

Table 1.

Categorization of reviewed articles relating to curcumin or ursolic acid and prostate cancer.

Phytonutrient	Total	Absorption & bioavailability	Pathways & effects	In vitro	In vivo	In vivo (Human)
Curcumin	219	58^a	173^a	198^b	61^b	8
Ursolic Acid	26	4^a	24^a	24^b	6^b	0
Total	245	62	197	222	67	8

12 articles on curcumin and 2 articles on ursolic acid reported data on both Absorption & Bioavailability and Pathways & Effects outcomes categories.

40 articles on curcumin and 5 articles on ursolic acid conducted studies both in vitro or in vivo. One article on ursolic acid did not report whether study was conducted in vitro or in vivo.

Table 2.

Human studies evaluating the effects of curcumin (n = 8) in prostate cancer.^a

	Study ID	Year	Study type	Randomized	Inclusion criteria	Study size	Intervention	Curcumin dose	Time treated	Comparisons	Outcomes category	Outcomes	Safety
12	Choi YH, PMID: 30671976	2019	Prospective	Yes	PCa with intermittent androgen deprivation	91 (1:1)	Curcumin	1440 mg/day	6 months	Placebo	Pathways and effects	PSA elevation suppressed	Safe and well tolerated
13	Saadipoor A, PMID: 30427093	2019	Prospective	Yes	PCa and candidate for IMRT	64 (1:1)	Nanocurcumin	120 mg/day	3 days before and during RT	Placebo	Pathways and effects	No outcome difference detected	Well tolerated
14	Greil R, PMID: 30074076	2018	Prospective	No	Metastatic cancer	32 (2 PCa)	Lipocurc™ (liposomal curcumin)	100–300 mg/m²	8 weeks	None	Absorption and bioavailability	Maximum tolerated dose	Well tolerated
15	Ledda A, PMID: 29028078	2017	Prospective	No	PCa or bladder cancer	61 (26:35)	Oncotris (curcumin, cordyceps, and astaxanthin)	Unknown	6 weeks	Placebo	Pathways and effects	PSA reduced	No adverse effects
16	Ried K, PMID: 28843267	2017	Observational	N/A	PCa (or other cancer)	542 (5 PCa)	Curcumin	Unknown	Unknown	None	Pathways and effects	CTC count reduction	No adverse effects
17	Mahammedi H, PMID: 26771576	2016	Prospective	No	Castration-resistant PCa with rising PSA	26	Curcumin/docetaxel/prednisone	6000 mg/day	6 days	None	Pathways and effects	PSA reduction	No adverse effects and well tolerated
18	Hejazi J, PMID: 26771294	2016	Prospective	Yes	PCa with EBRT	40 (1:1)	Curcumin	3000 mg/day	During RT	Placebo	Pathways and effects	PSA elevation suppressed	No adverse effects
19	Ide H, PMID: 20503397	2010	Prospective	Yes	Negative prostate biopsy with no PIN	85 (1:1)	Curcumin/isoflavones	100 mg	6 months	Placebo	Pathways and effects	PSA reduced	No adverse effects

There are no studies investigating the impact of ursolic acid on prostate cancer.

Figure 3.

Year of study published involving curcumin (n = 219) and ursolic acid (n = 26) and prostate cancer. Counts and percentage of publication years can be found in Supplemental Table 1.

Figure 4.

Countries of origin world map distribution of published studies involving: (a) curcumin and (b) ursolic acid and prostate cancer. *Seven articles on curcumin reported more than one country of origin. Counts and percentage of publication countries of origin can be found in Supplemental Table 2.

Curcumin mechanism in prostate cancer

We identified 373 CURC-related studies with 5 duplicate articles and 94 reviews/comments/retractions were removed. Of the 274 articles remaining, 55 studies were excluded upon eligibility assessment due to no reference to CURC or PCa. Finally, 173 of the 219 articles relating to CURC and PCa reported data outcomes on the mechanistic pathways (Supplemental Table 3), which we used to perform descriptive and qualitative analysis.^{7,12,13,15–184} The word cloud of the most common pathways affected in prostate cancer is displayed in Figure 5(a) and Supplemental Table 4, with the pathway involving NF-κB as the most common (n = 25/173, 14.5%).

Figure 5.

Word cloud of curcumin and ursolic acid mechanistic pathways in prostate cancer individually and combined. (a) Word cloud of most common molecular and cellular pathways from articles reporting on the pathways and effects of curcumin (n = 173) in prostate cancer. Larger words signify greater overlap and common pathways across all articles. Counts and percentage of most common pathways can be found in Supplemental Table 4. Two articles (1.2%) did not report any specific effects. (b) Word cloud of most common molecular and cellular pathways from articles reporting on the pathways and effects of ursolic acid (n = 24) in prostate cancer. Larger words signify greater overlap and common pathways across all articles. Counts and percentage of most common pathways can be found in Supplemental Table 6. (c) Word cloud of most common molecular and cellular pathways from articles reporting on the pathways and effects (n = 197) of both curcumin (n = 173) and ursolic acid (n = 24) in prostate cancer. Larger words signify greater overlap and common pathways across all articles. Counts and percentage of most common pathways can be found in Supplemental Table 7.

Ursolic acid mechanism in prostate cancer

We identified 41 UA-related studies with four duplicate articles and four reviews were removed. Of the 33 articles remaining, 7 studies were excluded upon eligibility assessment due to no reference to UA or PCa. Finally, 24 of the 26 articles relating to UA and PCa reported data outcomes on the mechanistic pathways (Supplemental Table 5), which we used to perform descriptive and qualitative analysis.^7,185–207 The word cloud of the most common pathways affected in prostate cancer is displayed Figure 5(b) and Supplemental Table 6, with the pathway involving caspase 3/caspase 9 as the most common (n = 10/24, 41.7%). Specific to humans, five prospective studies reported curcumin effects on prostate-specific antigen (PSA) reduction.

Combination of curcumin and ursolic acid

In order to identify the best pathway described in the literature using both compounds we performed a third word cloud analysis (Figure 5(c)) with the combination of all articles within the review that reported data outcomes on mechanistic pathways (n = 197; CURC = 173, UA = 24). The most common combined mechanistic pathways affecting prostate cancer for both CURC and UA involved NF-κB (n = 28/197, 14.2%), Akt (n = 22/197, 11.2%), and androgen (n = 19/197, 9.6%) (Supplemental Table 7).

Curcumin bioavailability and prostate cancer

Upon review of study outcome categories for CURC-related studies, a total of 58 (58/219, 26.5%) articles evaluated the absorption or bioavailability^{14,27,29,32,38,57,73,76,81,84,87,90,135,208–252} (Supplemental Table 8). Many studies investigated the delivery of curcumin to increase absorption by using nanoparticles or nanocapsules (n = 27/58, 46.6%) or liposomes (n = 6/58, 10.3%). While one human study assessed the pharmacokinetics of curcumin, specifically liposomal curcumin, in the blood (Table 2),¹⁰ none of the eight human studies measured or reported curcumin uptake into normal or cancerous prostate cells. However, all eight human studies investigated varying curcumin dosing regimens from 100 to 6000 mg/day spanning timeframes from 6 days to 6 months in men with prostate cancer (Table 2).

Ursolic acid bioavailability and prostate cancer

Upon review of study outcome categories for UA-related studies, a total of 4 (4/26, 15.4%) articles evaluated the absorption or bioavailability^{197,201,253,254} (Supplemental Table 9). Only one study investigated the delivery of ursolic acid to increase absorption by using liposomes (n = 1/4, 25%).²⁵⁴ In contrast to curcumin, there were no articles identified involving human ursolic acid bioavailability in men with prostate cancer.

Discussion

Our systematic review and qualitative analysis noted NF-κB as the primary target to investigate the synergistic mechanism of action of curcumin and ursolic acid in prostate cancer. Nuclear factor-kappa B (NF-κB) is a transcription factor essential for inflammatory responses by activating multiple downstream targets²⁵⁵ and is now a known cancer therapeutic target.²⁵⁶ NF-κB has an established communication pathway with androgen receptors, which agrees with our qualitative analysis assessment.²⁵⁷ In addition to androgens as a driver of prostate cancer, NF-κB participates in inflammatory cross-talk, which also is a driver of prostate cancer progression.^258,259 Additionally, NF-κB is implicated in prostate cancer progression to androgen independence in advanced cancer.^260,261 From our review, we understand that curcumin and ursolic acid are known to reduce the inflammatory pathway in prostate cancer, likely through NF-κB. Unfortunately, various barriers continue to exist regarding the translation of these compounds as a therapeutic option in prostate cancer.

Despite the growing interest in using dietary supplements for cancer, drug bioavailability remains a major barrier of using natural products for adjunctive cancer therapy. A report in 2009 noted 63% of prostate cancer patients surveyed (n = 827) reported using dietary supplements.²⁶² In 1994, the Dietary Supplement Health and Education Act gave the FDA the authority to regulate dietary supplements, which did not require pre-market approval, yet does allow the FDA to investigate a supplement for health safety or false claims.²⁶³ Therefore, dietary supplements can be approved by only showing safety, while efficacy is de-emphasized. Patients commonly request dietary supplements as potential adjuvant therapy, but the research severely lacks test efficacy, particularly in prostate cancer. For example, we investigated human studies of curcumin (n = 8) and ursolic acid (n = 0) compared to over 200 such studies using animals or cell lines. While some groups are investigating the delivery of curcumin in PCa cell lines using nanoparticles and liposomes, we did not identify any studies investigating the uptake of these phytonutrients specifically in prostate cancer cells in humans. Shown through our review with the majority of studies investigating the molecular mechanisms of these phytonutrients in prostate cancer and becoming increasingly uncovered, more data on bioavailability is now important. Based on the promising data from Lodi et al.,⁷ a translational science approach using new drug development techniques is needed to enhance curcumin and ursolic acid absorption, show targeted mechanism effects, and prove efficacy in human prostate cancer patients.

Other highly ranked molecular pathways from our analysis included Akt (protein kinase B), androgen receptor, and apoptosis pathways (Figure 5). While the androgen receptor is highly studied and known in prostate cancer progression and current treatment, Akt plays a role in the PI3K/AKT pathway of tumorigenesis including apoptosis and proliferation of PCa cells as a part of the NF-κB axis.²⁶⁴ Therefore, with the Akt pathway shown to be studied in CURC and UA through our review in combination with NF-κB, these pathways should be further investigated to understand the exact axis points of the effects from CURC and UA. More importantly, these pathways should also be investigated within the tissues of human prostate cancers after exposure to curcumin and ursolic acid combined for their possible synergism.

We acknowledge the limitations of this study in that not all the studies are performed in a similar manner. We used a novel technique for analysis of our systematic review because the nature of non-human basic science does not allow for standard tools for effect size. Using the primary findings from the abstracts or results section, we utilized the NVivo software to identify the most common terms. Also, the pathway studies were not random in many manuscripts. Investigators usually choose a particular pathway to investigate and because NF-κB is a key pathway for many cancers, this pathway may have been selected more so than other pathways.

Conclusions

We identified ample in vitro studies involving the effects of CURC with fewer in vitro studies involving the effects of UA in prostate cancer. We use this review to identify a target pathway of the synergistic effects of curcumin and ursolic acid and show that NF-κB and Akt to be the most investigated pathway effect in prostate cancer. Our review highlights the limited human studies and data of these phytonutrients’ bioavailability and effects in prostate cancer. With the lack of possible treatment for men with low-grade prostate cancer, this review identifies areas of investigation on CURC and UA treatment outcomes in prostate cancer human clinical trials.

Supplemental Material

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Footnotes

Acknowledgements

None.

Authors’ contribution

MAL contributed to the review conception, design, and supervision. BDB contributed to search, acquisition, review, and collection of data. BDB and MAL contributed to the analysis of data. BDB, AS, JD, and MAL contributed to the writing, review, and/or revision of the manuscript and approved the final manuscript.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research was supported by a generous gift from Los Padres Foundation.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

ORCID iD

Benjamin D Besasie

Availability of data and materials

The authors confirm that the data supporting the findings of this study are available within the article and/or its supplemental materials.

Supplemental material

Supplemental material for this article is available online.

References

Siegel

Miller

Jemal

. Cancer statistics, 2019. CA Cancer J Clin 2019; 69: 7–34.

Carroll

Mohler

. NCCN guidelines updates: prostate cancer and prostate cancer early detection. J Natl Compr Canc Netw 2018; 16: 620–623.

Eastham

Auffenberg

Barocas

, et al. Clinically localized prostate cancer: AUA/ASTRO guideline, Part I: introduction, risk assessment, staging, and risk-based management. J Urol 2022; 208: 10–18.

Sanda

Cadeddu

Kirkby

, et al. Clinically localized prostate cancer: AUA/ASTRO/SUO guideline. Part I: risk stratification, shared decision making, and care options. J Urol 2018; 199: 683–690.

Goldberg

Klaassen

Chandrasekar

, et al. Preventing clinical progression and need for treatment in patients on active surveillance for prostate cancer. Curr Opin Urol 2018; 28: 46–54.

Deguchi

. Curcumin targets in inflammation and cancer. Endocr Metab Immune Disord Drug Targets 2015; 15: 88–96.

Lodi

Saha

, et al. Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism. NPJ Precis Oncol 2017; 1: 30.

Anand

Kunnumakkara

Newman

, et al. Bioavailability of curcumin: problems and promises. Mol Pharm 2007; 4: 807–818.

Mlala

Oyedeji

Gondwe

, et al. Ursolic acid and its derivatives as bioactive agents. Molecules 2019; 24: 2751.

10.

Liberati

Altman

Tetzlaff

, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009; 339: b2700.

11.

Hayden

Côté

Bombardier

. Evaluation of the quality of prognosis studies in systematic reviews. Ann Intern Med 2006; 144: 427–437.

12.

Choi

Han

Kim

, et al. A randomized, double-blind, placebo-controlled trial to evaluate the role of curcumin in prostate cancer patients with intermittent androgen deprivation. Prostate 2019; 79: 614–621.

13.

Saadipoor

Razzaghdoust

Simforoosh

, et al. Randomized, double-blind, placebo-controlled phase II trial of nanocurcumin in prostate cancer patients undergoing radiotherapy. Phytother Res 2019; 33: 370–378.

14.

Greil

Greil-Ressler

Weiss

, et al. A phase 1 dose-escalation study on the safety, tolerability and activity of liposomal curcumin (Lipocurc™) in patients with locally advanced or metastatic cancer. Cancer Chemother Pharmacol 2018; 82: 695–706.

15.

Ledda

Belcaro

Dugall

, et al. A natural pharma standard supplement formulation to control treatment-related toxicity and oxidative stress in genitourinary cancer: a preliminary study. Eur Rev Med Pharmacol Sci 2017; 21: 4196–4202.

16.

Ried

Eng

Sali

. Screening for circulating tumour cells allows early detection of cancer and monitoring of treatment effectiveness: an observational study. Asian Pac J Cancer Prev 2017; 18: 2275–2285.

17.

Mahammedi

Planchat

Pouget

, et al. The new combination docetaxel, prednisone and curcumin in patients with castration-resistant prostate cancer: a pilot phase II study. Oncology 2016; 90: 69–78.

18.

Hejazi

Rastmanesh

Taleban

, et al. Effect of curcumin supplementation during radiotherapy on oxidative status of patients with prostate cancer: a double blinded, randomized, placebo-controlled study. Nutr Cancer 2016; 68: 77–85.

19.

Ide

Tokiwa

Sakamaki

, et al. Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate-specific antigen. Prostate 2010; 70: 1127–1133.

20.

Ocasio-Malavé

Donate

Sánchez

, et al. Synthesis of novel 4-boc-piperidone chalcones and evaluation of their cytotoxic activity against highly-metastatic cancer cells. Bioorg Med Chem Lett 2020; 30: 126760.

21.

Katta

Srivastava

Thangapazham

, et al. Curcumin-gene expression response in hormone dependent and independent metastatic prostate cancer cells. Int J Mol Sci 2019; 20: 4891.

22.

Rodríguez Castaño

Parween

Pandey

. Bioactivity of curcumin on the cytochrome P450 enzymes of the steroidogenic pathway. Int J Mol Sci 2019; 20: 4606.

23.

Yang

Liu

, et al. The chromatin remodeling protein BRG1 links ELOVL3 trans-activation to prostate cancer metastasis. Biochim Biophys Acta Gene Regul Mech 2019; 1862: 834–845.

24.

Zhu

Zheng

Huang

, et al. Modulation of miR-34a in curcumin-induced antiproliferation of prostate cancer cells. J Cell Biochem 2019; 120: 15616–15624.

25.

Guo

, et al. Evaluation of biophysical as well as biochemical potential of curcumin and resveratrol during prostate cancer. J Drug Target 2020; 28: 41–45.

26.

Doush

Surani

Navarro-Corcuera

, et al. SP1 and RARα regulate AGAP2 expression in cancer. Sci Rep 2019; 9: 390.

27.

Belluti

Orteca

Semeghini

, et al. Potent anti-cancer properties of phthalimide-based curcumin derivatives on prostate tumor cells. Int J Mol Sci 2018; 20: 28.

28.

Mapoung

Suzuki

Fuji

, et al. Cyclohexanone curcumin analogs inhibit the progression of castration-resistant prostate cancer in vitro and in vivo. Cancer Sci 2019; 110: 596–607.

29.

Vellampatti

Chandrasekaran

Mitta

, et al. Metallo-curcumin-conjugated DNA complexes induces preferential prostate cancer cells cytotoxicity and pause growth of bacterial cells. Sci Rep 2018; 8: 14929.

30.

Luo

Tian

Chou

, et al. Targeting the androgen receptor (AR) with AR degradation enhancer ASC-J9® led to increase docetaxel sensitivity via suppressing the p21 expression. Cancer Lett 2019; 444: 35–44.

31.

Fort

Trinidad Barnech

Dourron

, et al. Isolation and structural characterization of bioactive molecules on prostate cancer from Mayan traditional medicinal plants. Pharmaceuticals 2018; 11: 78.

32.

Plyduang

Armiñán

Movellan

, et al. Polyacetal-based combination therapy for the treatment of prostate cancer. Macromol Rapid Commun 2018; 39: e1800265.

33.

Zhao

Zhou

, et al. Curcumin suppressed the prostate cancer by inhibiting JNK pathways via epigenetic regulation. J Biochem Mol Toxicol 2018; 32: e22049.

34.

Lin

Luo

Sun

, et al. ASC-J9(®) suppresses prostate cancer cell invasion via altering the sumoylation-phosphorylation of stat3. Cancer Lett 2018; 425: 21–30.

35.

Cheng

Huang

Tai

, et al. Maspin enhances the anticancer activity of curcumin in hormone-refractory prostate cancer cells. Anticancer Res 2018; 38: 863–870.

36.

Ide

Noguchi

, et al. Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer. Cancer Sci 2018; 109: 1230–1238.

37.

Guo

, et al. Curcumin derivative epigenetically reactivates Nrf2 antioxidative stress signaling in mouse prostate cancer TRAMP C1 cells. Chem Res Toxicol 2018; 31: 88–96.

38.

Chen

Nimick

Cridge

, et al. Anticancer potential of novel curcumin analogs towards castrate-resistant prostate cancer. Int J Oncol 2018; 52: 579–588.

39.

Ramya

PVS

Guntuku

Angapelly

, et al. Synthesis and biological evaluation of curcumin inspired imidazo[1,2-a]pyridine analogues as tubulin polymerization inhibitors. Eur J Med Chem 2018; 143: 216–231.

40.

Zhang

Zheng

Shen

, et al. Curcumin suppresses in vitro proliferation and invasion of human prostate cancer stem cells by modulating DLK1-DIO3 imprinted gene cluster MicroRNAs. Genet Test Mol Biomarkers 2018; 22: 43–50.

41.

Liu

Chi

Chen

, et al. Curcumin suppresses proliferation and in vitro invasion of human prostate cancer stem cells by ceRNA effect of miR-145 and lncRNA-ROR. Gene 2017; 631: 29–38.

42.

Rivera

Ramos

Rodríguez-Valentín

, et al. Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells. PLoS One 2017; 12: e0179587.

43.

Wang

Sun

, et al. Preclinical study using malat1 small interfering RNA or androgen receptor splicing variant 7 degradation enhancer ASC-J9(®) to suppress enzalutamide-resistant prostate cancer progression. Eur Urol 2017; 72: 835–844.

44.

Liu

Wang

, et al. Curcumin sensitizes prostate cancer cells to radiation partly via epigenetic activation of miR-143 and miR-143 mediated autophagy inhibition. J Drug Target 2017; 25: 645–652.

45.

Cao

Feng

, et al. Curcumin inhibits prostate cancer by targeting PGK1 in the FOXD3/miR-143 axis. Cancer Chemother Pharmacol 2017; 79: 985–994.

46.

Rodriguez-Garcia

Hevia

Mayo

, et al. Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells. Redox Biol 2017; 12: 634–647.

47.

Yang

Wang

, et al. Curcumin induces apoptosis and protective autophagy in castration-resistant prostate cancer cells through iron chelation. Drug Des Devel Ther 2017; 11: 431–439.

48.

Banerjee

Singh

Chowdhury

, et al. Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer. Front Biosci 2017; 9: 235–245.

49.

Yang

Wang

Zhang

, et al. Curcumin inhibits the survival and metastasis of prostate cancer cells via the Notch-1 signaling pathway. APMIS 2017; 125: 134–140.

50.

Sri Ramya

Angapelly

Guntuku

, et al. Synthesis and biological evaluation of curcumin inspired indole analogues as tubulin polymerization inhibitors. Eur J Med Chem 2017; 127: 100–114.

51.

Chen

Zhou

Zhong

, et al. Increased intracellular reactive oxygen species mediates the anti-cancer effects of WZ35 via activating mitochondrial apoptosis pathway in prostate cancer cells. Prostate 2017; 77: 489–504.

52.

Fehl

Ahmed

. Curcumin promotes the oncoltyic capacity of vesicular stomatitis virus for the treatment of prostate cancers. Virus Res 2017; 228: 14–23.

53.

Sha

Wang

, et al. Curcumin induces G0/G1 arrest and apoptosis in hormone independent prostate cancer DU-145 cells by down regulating notch signaling. Biomed Pharmacother 2016; 84: 177–184.

54.

Zhang

Wang

Perez

, et al. Design, synthesis, and biological evaluation of 1,9-diheteroarylnona-1,3,6,8-tetraen-5-ones as a new class of anti-prostate cancer agents. Bioorg Med Chem 2016; 24: 4692–4700.

55.

Mandalapu

Saini

Gupta

, et al. Synthesis and biological evaluation of some novel triazole hybrids of curcumin mimics and their selective anticancer activity against breast and prostate cancer cell lines. Bioorg Med Chem Lett 2016; 26: 4223–4232.

56.

Nagahama

Utsumi

Kumano

, et al. Discovery of a new function of curcumin which enhances its anticancer therapeutic potency. Sci Rep 2016; 6: 30962.

57.

Jayaprakasha

Chidambara Murthy

Patil

. Enhanced colon cancer chemoprevention of curcumin by nanoencapsulation with whey protein. Eur J Pharmacol 2016; 789: 291–300.

58.

Zhou

Zhao

, et al. Pyridine analogues of curcumin exhibit high activity for inhibiting CWR-22Rv1 human prostate cancer cell growth and androgen receptor activation. Oncol Lett 2016; 11: 4160–4166.

59.

Wang

Lin

, et al. ASC-J9(®) suppresses castration resistant prostate cancer progression via degrading the enzalutamide-induced androgen receptor mutant AR-F876L. Cancer Lett 2016; 379: 154–160.

60.

Sharma

Kumar

Mohanty

, et al. Sensitization of androgen refractory prostate cancer cells to anti-androgens through re-expression of epigenetically repressed androgen receptor - synergistic action of quercetin and curcumin. Mol Cell Endocrinol 2016; 431: 12–23.

61.

Wen

Tian

Niu

, et al. ASC-J9(®), and not casodex or enzalutamide, suppresses prostate cancer stem/progenitor cell invasion via altering the EZH2-STAT3 signals. Cancer Lett 2016; 376: 377–386.

62.

Pung

, et al. Epigenetics reactivation of Nrf2 in prostate TRAMP C1 cells by curcumin analogue FN1. Chem Res Toxicol 2016; 29: 694–703.

63.

Wen

Niu

Lee

, et al. Targeting fatty acid synthase with ASC-J9 suppresses proliferation and invasion of prostate cancer cells. Mol Carcinog 2016; 55: 2278–2290.

64.

Lin

Liu

, et al. Curcumin mediates reversion of HGF-induced epithelial-mesenchymal transition via inhibition of c-Met expression in DU145 cells. Oncol Lett 2016; 11: 1499–1505.

65.

Wang

Zhang

Chen

, et al. Synthesis and evaluation of 1,7-diheteroarylhepta-1,4,6-trien-3-ones as curcumin-based anticancer agents. Eur J Med Chem 2016; 110: 164–180.

66.

Kang

Kook

, et al. Theracurmin® efficiently inhibits the growth of human prostate and bladder cancer cells via induction of apoptotic cell death and cell cycle arrest. Oncol Rep 2016; 35: 1463–1472.

67.

Huang

Chen

, et al. Combination of α-tomatine and curcumin inhibits growth and induces apoptosis in human prostate cancer cells. PLoS One 2015; 10: e0144293.

68.

Zhang

Chen

Zou

, et al. Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells. BMC Cancer 2015; 15: 866.

69.

Long

Zhang

, et al. Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mtor/HIF-1α signaling. Int J Oncol 2015; 47: 2064–2072.

70.

Yang

Ning

Peng

, et al. Effect of curcumin on Bcl-2 and Bax expression in nude mice prostate cancer. Int J Clin Exp Pathol 2015; 8: 9272–9278.

71.

Hong

Lee

Choi

. Effect of curcumin on the interaction between androgen receptor and wnt/β-catenin in LNCaP xenografts. Korean J Urol 2015; 56: 656–665.

72.

Chen

Zhang

, et al. A new class of hybrid anticancer agents inspired by the synergistic effects of curcumin and genistein: design, synthesis, and anti-proliferative evaluation. Bioorg Med Chem Lett 2015; 25: 4553–4556.

73.

Yan

Wang

Zhang

, et al. Targeted nanomedicine for prostate cancer therapy: docetaxel and curcumin co-encapsulated lipid-polymer hybrid nanoparticles for the enhanced anti-tumor activity in vitro and in vivo. Drug Deliv 2016; 23: 1757–1762.

74.

Lee

Chien

Chow

, et al. Nonautophagic cytoplasmic vacuolation death induction in human PC-3M prostate cancer by curcumin through reactive oxygen species -mediated endoplasmic reticulum stress. Sci Rep 2015; 5: 10420.

75.

Xiang

Zhang

, et al. Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-κB/p65 and MUC1-C. J Exp Clin Cancer Res 2015; 34: 46.

76.

Chen

Luo

, et al. Synthesis and assessment of the antioxidant and antitumor properties of asymmetric curcumin analogues. Eur J Med Chem 2015; 93: 461–469.

77.

Linnewiel-Hermoni

Khanin

Danilenko

, et al. The anti-cancer effects of carotenoids and other phytonutrients resides in their combined activity. Arch Biochem Biophys 2015; 572: 28–35.

78.

Kim

Datta

, et al. Hydrazinobenzoylcurcumin inhibits androgen receptor activity and growth of castration-resistant prostate cancer in mice. Oncotarget 2015; 6: 6136–6150.

79.

Fernández-Martínez

Carmena

Bajo

, et al. VIP induces NF-κB1-nuclear localisation through different signalling pathways in human tumour and non-tumour prostate cells. Cell Signal 2015; 27: 236–244.

80.

Eom

Lee

Kim

, et al. Synergistic effect of curcumin on epigallocatechin gallate-induced anticancer action in PC3 prostate cancer cells. BMB Rep 2015; 48: 461–466.

81.

Wang

Chung

, et al. Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells. RSC Adv 2014; 4: 35242–35250.

82.

Mathur

Abd Elmageed

Liu

, et al. Subverting ER-stress towards apoptosis by nelfinavir and curcumin coexposure augments docetaxel efficacy in castration resistant prostate cancer cells. PLoS One 2014; 9: e103109.

83.

Zhou

Ding

, et al. Curcumin analogues with high activity for inhibiting human prostate cancer cell growth and androgen receptor activation. Mol Med Rep 2014; 10: 1315–1322.

84.

Yallapu

Khan

Maher

, et al. Anti-cancer activity of curcumin loaded nanoparticles in prostate cancer. Biomaterials 2014; 35: 8635–8648.

85.

Dorai

Diouri

O'Shea

, et al. Curcumin inhibits prostate cancer bone metastasis by up-regulating bone morphogenic protein-7 in vivo. J Cancer Ther 2014; 5: 369–386.

86.

Jing

Zhao

, et al. Curcumin inhibits expression of inhibitor of DNA binding 1 in PC3 cells and xenografts. Asian Pac J Cancer Prev 2014; 15: 1465–1470.

87.

Luo

Zhou

, et al. A monocarbonyl analogue of curcumin, 1,5-bis(3-hydroxyphenyl)-1,4-pentadiene-3-one (Ca 37), exhibits potent growth suppressive activity and enhances the inhibitory effect of curcumin on human prostate cancer cells. Apoptosis 2014; 19: 542–553.

88.

Gupta

Zhou

Chellaiah

. Osteopontin and MMP9: associations with VEGF expression/secretion and angiogenesis in PC3 prostate cancer cells. Cancers 2013; 5: 617–638.

89.

Piccolella

Crippa

Messi

, et al. Modulators of estrogen receptor inhibit proliferation and migration of prostate cancer cells. Pharmacol Res 2014; 79: 13–20.

90.

Harada

Giorgio

Harris

, et al. Diamide linked γ-cyclodextrin dimers as molecular-scale delivery systems for the medicinal pigment curcumin to prostate cancer cells. Mol Pharm 2013; 10: 4481–4490.

91.

Botchkina

Zuniga

Rowehl

, et al. Prostate cancer stem cell-targeted efficacy of a new-generation taxoid, SBT-1214 and novel polyenolic zinc-binding curcuminoid, CMC2.24. PLoS One 2013; 8: e69884.

92.

Zhou

Zhang

Conney

, et al. Synthesis and evaluation of curcumin-related compounds containing benzyl piperidone for their effects on human cancer cells. Chem Pharm Bull 2013; 61: 1149–1155.

93.

Yang

Yue

Sims

, et al. The curcumin analog EF24 targets NF-κB and miRNA-21, and has potent anticancer activity in vitro and in vivo. PLoS One 2013; 8: e71130.

94.

Lin

Izumi

Lee

, et al. Anti-androgen receptor ASC-J9 versus anti-androgens MDV3100 (enzalutamide) or casodex (bicalutamide) leads to opposite effects on prostate cancer metastasis via differential modulation of macrophage infiltration and STAT3-CCL2 signaling. Cell Death Dis 2013; 4: e764.

95.

Guo

, et al. Curcumin induces cell cycle arrest and apoptosis of prostate cancer cells by regulating the expression of ikappaBalpha, c-Jun and androgen receptor. Pharmazie 2013; 68: 431–434.

96.

Lin

Lee

Niu

, et al. Differential androgen deprivation therapies with anti-androgens casodex/bicalutamide or MDV3100/enzalutamide versus anti-androgen receptor ASC-J9(R) lead to promotion versus suppression of prostate cancer metastasis. J Biol Chem 2013; 288: 19359–19369.

97.

Wei

Zhou

Wang

, et al. Effects of pyridine analogs of curcumin on growth, apoptosis and NF-κB activity in prostate cancer PC-3 cells. Anticancer Res 2013; 33: 1343–1350.

98.

Cheng

Chen

Lin

, et al. Curcumin-targeting pericellular serine protease matriptase role in suppression of prostate cancer cell invasion, tumor growth, and metastasis. Cancer Prev Res 2013; 6: 495–505.

99.

Kang

Park

Lee

, et al. Crosstalk from survival to necrotic death coexists in DU-145 cells by curcumin treatment. Cell Signal 2013; 25: 1288–1300.

100.

Lai

Huang

Chang

, et al. New therapeutic approach to suppress castration-resistant prostate cancer using ASC-J9 via targeting androgen receptor in selective prostate cells. Am J Pathol 2013; 182: 460–473.

101.

Chen

Corteling

Stevanato

, et al. Polyphenols inhibit indoleamine 3,5-dioxygenase-1 enzymatic activity–a role of immunomodulation in chemoprevention. Discov Med 2012; 14: 327–333.

102.

Killian

Kronski

Michalik

, et al. Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and -2. Carcinogenesis 2012; 33: 2507–2519.

103.

Bao

Ahmad

Kong

, et al. Hypoxia induced aggressiveness of prostate cancer cells is linked with deregulated expression of VEGF, IL-6 and miRNAs that are attenuated by CDF. PLoS One 2012; 7: e43726.

104.

Hung

Lin

, et al. Demethoxycurcumin modulates prostate cancer cell proliferation via AMPK-induced down-regulation of HSP70 and EGFR. J Agric Food Chem 2012; 60: 8427–8434.

105.

Wei

Cui

, et al. Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells. Oncol Lett 2012; 4: 279–284.

106.

Lee

Yeh

, et al. New therapy targeting differential androgen receptor signaling in prostate cancer stem/progenitor vs. non-stem/progenitor cells. J Mol Cell Biol 2013; 5: 14–26.

107.

Pramanik

Campbell

Das

, et al. A composite polymer nanoparticle overcomes multidrug resistance and ameliorates doxorubicin-associated cardiomyopathy. Oncotarget 2012; 3: 640–650.

108.

Guo

Yin

Dong

, et al. Enhanced apoptotic effects by the combination of curcumin and methylseleninic acid: potential role of mcl-1 and FAK. Mol Carcinog 2013; 52: 879–889.

109.

Shi

Wada

Ohkoshi

, et al. Antitumor agents 290. Design, synthesis, and biological evaluation of new LNCaP and PC-3 cytotoxic curcumin analogs conjugated with anti-androgens. Bioorg Med Chem 2012; 20: 4020–4031.

110.

Zhang

Zhao

, et al. Demethoxycurcumin inhibits cell proliferation, migration and invasion in prostate cancer cells. Oncol Rep 2012; 28: 85–90.

111.

Wei

Zheng

, et al. Synthesis and evaluation of curcumin-related compounds for anticancer activity. Eur J Med Chem 2012; 53: 235–245.

112.

Sundram

Chauhan

Ebeling

, et al. Curcumin attenuates β-catenin signaling in prostate cancer cells through activation of protein kinase d1. PLoS One 2012; 7: e35368.

113.

Teiten

Gaigneaux

Chateauvieux

, et al. Identification of differentially expressed proteins in curcumin-treated prostate cancer cell lines. OMICS 2012; 16: 289–300.

114.

Yamashita

Lai

Chuang

, et al. ASC-J9 suppresses castration-resistant prostate cancer growth through degradation of full-length and splice variant androgen receptors. Neoplasia 2012; 14: 74–83.

115.

Shah

Prasad

Knudsen

. Targeting pioneering factor and hormone receptor cooperative pathways to suppress tumor progression. Cancer Res 2012; 72: 1248–1259.

116.

Farooqi

Bhatti

Rana

, et al. Shattering the underpinnings of neoplastic architecture in LNCap: synergistic potential of nutraceuticals in dampening PDGFR/EGFR signaling and cellular proliferation. J Exp Ther Oncol 2011; 9: 201–206.

117.

Shu

Khor

Lee

, et al. Epigenetic cpg demethylation of the promoter and reactivation of the expression of neurog1 by curcumin in prostate LNCaP cells. AAPS J 2011; 13: 606–614.

118.

Chung

Tsui

Feng

, et al. Curcumin provides potential protection against the activation of hypoxia and prolyl 4-hydroxylase inhibitors on prostate-specific antigen expression in human prostate carcinoma cells. Mol Nutr Food Res 2011; 55: 1666–1676.

119.

Liu

Wang

, et al. Anti-tumor activity of curcumin against androgen-independent prostate cancer cells via inhibition of NF-κB and AP-1 pathway in vitro. J Huazhong Univ Sci Technol Med Sci 2011; 31: 530.

120.

Fajardo

MacKenzie

, et al. The curcumin analog ca27 down-regulates androgen receptor through an oxidative stress mediated mechanism in human prostate cancer cells. Prostate 2012; 72: 612–625.

121.

Khor

Huang

, et al. Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter cpgs demethylation. Biochem Pharmacol 2011; 82: 1073–1078.

122.

Kong

Wang

, et al. Inactivation of AR/TMPRSS2-ERG/Wnt signaling networks attenuates the aggressive behavior of prostate cancer cells. Cancer Prev Res 2011; 4: 1495–1506.

123.

Teiten

Gaascht

Cronauer

, et al. Anti-proliferative potential of curcumin in androgen-dependent prostate cancer cells occurs through modulation of the Wingless signaling pathway. Int J Oncol 2011; 38: 603–611.

124.

Lamson

Plaza

, et al. The vitamin C:vitamin K3 system - enhancers and inhibitors of the anticancer effect. Altern Med Rev 2010; 15: 345–351.

125.

Ide

, et al. Testosterone augments polyphenol-induced DNA damage response in prostate cancer cell line, LNCaP. Cancer Sci 2011; 102: 468–471.

126.

Wan

Yang

Zhou

, et al. Evaluation of curcumin acetates and amino acid conjugates as proteasome inhibitors. Int J Mol Med 2010; 26: 447–455.

127.

Choi

Lim

Hong

. Curcumin interrupts the interaction between the androgen receptor and Wnt/β-catenin signaling pathway in LNCaP prostate cancer cells. Prostate Cancer Prostatic Dis 2010; 13: 343–349.

128.

Slusarz

Shenouda

Sakla

, et al. Common botanical compounds inhibit the hedgehog signaling pathway in prostate cancer. Cancer Res 2010; 70: 3382–3390.

129.

Hilchie

Furlong

Sutton

, et al. Curcumin-induced apoptosis in PC3 prostate carcinoma cells is caspase-independent and involves cellular ceramide accumulation and damage to mitochondria. Nutr Cancer 2010; 62: 379–389.

130.

Fernández-Martínez

Bajo

Valdehita

, et al. Multifunctional role of VIP in prostate cancer progression in a xenograft model: suppression by curcumin and COX-2 inhibitor NS-398. Peptides 2009; 30: 2357–2364.

131.

Zhou

Geng

Shi

, et al. Design and synthesis of androgen receptor antagonists with bulky side chains for overcoming antiandrogen resistance. J Med Chem 2009; 52: 5546–5550.

132.

Lin

Hutzen

Ball

, et al. New curcumin analogues exhibit enhanced growth-suppressive activity and inhibit AKT and signal transducer and activator of transcription 3 phosphorylation in breast and prostate cancer cells. Cancer Sci 2009; 100: 1719–1727.

133.

Piantino

Salvadori

Ayres

, et al. An evaluation of the anti-neoplastic activity of curcumin in prostate cancer cell lines. Int Braz J Urol 2009; 35: 354–360; discussion 361.

134.

Herman

Stadelman

Roselli

. Curcumin blocks CCL2-induced adhesion, motility and invasion, in part, through down-regulation of CCL2 expression and proteolytic activity. Int J Oncol 2009; 34: 1319–1327.

135.

Narayanan

Nargi

Randolph

, et al. Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice. Int J Cancer 2009; 125(1): 1–8.

136.

Andrzejewski

Deeb

Gao

, et al. Therapeutic efficacy of curcumin/TRAIL combination regimen for hormone-refractory prostate cancer. Oncol Res 2008; 17: 257–267.

137.

Fernández-Martínez

Bajo

Sánchez-Chapado

, et al. Vasoactive intestinal peptide behaves as a pro-metastatic factor in human prostate cancer cells. Prostate 2009; 69: 774–786.

138.

Valentini

Conforti

Crispini

, et al. Synthesis, oxidant properties, and antitumoral effects of a heteroleptic palladium(II) complex of curcumin on human prostate cancer cells. J Med Chem 2009; 52: 484–491.

139.

Santel

Pflug

Hemdan

, et al. Curcumin inhibits glyoxalase 1: a possible link to its anti-inflammatory and anti-tumor activity. PLoS One 2008; 3: e3508.

140.

Shen

Khor

, et al. Curcumin inhibits akt/mammalian target of rapamycin signaling through protein phosphatase-dependent mechanism. Mol Cancer Ther 2008; 7: 2609–2620.

141.

Thangapazham

Shaheduzzaman

Kim

, et al. Androgen responsive and refractory prostate cancer cells exhibit distinct curcumin regulated transcriptome. Cancer Biol Ther 2008; 7: 1427–1435.

142.

Thomas

Zhong

Zhou

, et al. EF24, a novel curcumin analog, disrupts the microtubule cytoskeleton and inhibits HIF-1. Cell Cycle 2008; 7: 2409–2417.

143.

Tsui

Feng

Lin

, et al. Curcumin blocks the activation of androgen and interlukin-6 on prostate-specific antigen expression in human prostatic carcinoma cells. J Androl 2008; 29: 661–668.

144.

Barve

Khor

Hao

, et al. Murine prostate cancer inhibition by dietary phytochemicals–curcumin and phenyethylisothiocyanate. Pharm Res 2008; 25: 2181–2189.

145.

Deng

, et al. [Curcumin inhibits the expression of vascular endothelial growth factor and androgen-independent prostate cancer cell line PC-3 in vitro]. Zhonghua Nan Ke Xue 2008; 14: 116–121.

146.

Shankar

Ganapathy

Chen

, et al. Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis. Mol Cancer 2008; 7: 16.

147.

Srivastava

Chen

Siddiqui

, et al. Linkage of curcumin-induced cell cycle arrest and apoptosis by cyclin-dependent kinase inhibitor p21(/WAF1/CIP1). Cell Cycle 2007; 6: 2953–2961.

148.

Shankar

Chen

Sarva

, et al. Curcumin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells: molecular mechanisms of apoptosis, migration and angiogenesis. J Mol Signal 2007; 2: 10.

149.

Shankar

Srivastava

. Involvement of Bcl-2 family members, phosphatidylinositol 3'-kinase/AKT and mitochondrial p53 in curcumin (diferulolylmethane)-induced apoptosis in prostate cancer. Int J Oncol 2007; 30: 905–918.

150.

Zhang

Hill

, et al. Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway. Cancer Res 2007; 67: 1988–1996.

151.

Zhang

, et al. Curcumin downregulates homeobox gene NKX3.1 in prostate cancer cell LNCaP. Acta Pharmacol Sin 2007; 28: 423–430.

152.

Shi

Chen

, et al. [Up-regulates the expression of maspin gene in prostate cancer cell line LNCaP]. Yao Xue Xue Bao 2006; 41: 1152–1156.

153.

Deeb

Jiang

Gao

, et al. Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1-6-heptadine-3,5-dione; C21H20O6] sensitizes human prostate cancer cells to tumor necrosis factor-related apoptosis-inducing ligand/Apo2L-induced apoptosis by suppressing nuclear factor-kappaB via inhibition of the prosurvival Akt signaling pathway. J Pharmacol Exp Ther 2007; 321: 616–625.

154.

Nonn

Duong

Peehl

. Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells. Carcinogenesis 2007; 28: 1188–1196.

155.

Guo

Chen

, et al. [Curcumin-induced the expression of inhibitor kappaBalpha protein in human prostate cancer cells]. Zhonghua Wai Ke Za Zhi 2006; 44: 1256–1259.

156.

Marcu

Jung

Lee

, et al. Curcumin is an inhibitor of p300 histone acetylatransferase. Med Chem 2006; 2: 169–174.

157.

Guo

Chen

, et al. [Curcumin-induced apoptosis in androgen-dependent prostate cancer cell line LNCaP in vitro]. Zhonghua Nan Ke Xue 2006; 12: 141–144.

158.

Deeb

Jiang

Gao

, et al. Chemosensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis. J Exp Ther Oncol 2005; 5: 81–91.

159.

Lin

Shi

, et al. Antitumor agents 247. New 4-ethoxycarbonylethyl curcumin analogs as potential antiandrogenic agents. Bioorg Med Chem 2006; 14: 2527–2534.

160.

Khor

Keum

Lin

, et al. Combined inhibitory effects of curcumin and phenethyl isothiocyanate on the growth of human PC-3 prostate xenografts in immunodeficient mice. Cancer Res 2006; 66: 613–621.

161.

Hong

Ahn

Bae

, et al. The effects of curcumin on the invasiveness of prostate cancer in vitro and in vivo. Prostate Cancer Prostatic Dis 2006; 9: 147–152.

162.

Yang

Zhang

Chen

, et al. [Inhibition of the expression of prostate specific antigen by curcumin]. Yao Xue Xue Bao 2005; 40: 800–803.

163.

Kim

Keum

, et al. Inhibition of EGFR signaling in human prostate cancer PC-3 cells by combination treatment with beta-phenylethyl isothiocyanate and curcumin. Carcinogenesis 2006; 27: 475–482.

164.

Polytarchou

Hatziapostolou

Papadimitriou

. Hydrogen peroxide stimulates proliferation and migration of human prostate cancer cells through activation of activator protein-1 and up-regulation of the heparin affin regulatory peptide gene. J Biol Chem 2005; 280: 40428–40435.

165.

Collado

Sánchez

Díaz-Laviada

, et al. Vasoactive intestinal peptide (VIP) induces c-fos expression in LNCaP prostate cancer cells through a mechanism that involves Ca2+ signalling. Implications in angiogenesis and neuroendocrine differentiation. Biochim Biophys Acta 2005; 1744: 224–233.

166.

Adams

Cai

Armstrong

, et al. EF24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. Anticancer Drugs 2005; 16: 263–275.

167.

Shenouda

Zhou

Browning

, et al. Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro. Nutr Cancer 2004; 49: 200–208.

168.

Deeb

Jiang

Gao

, et al. Curcumin sensitizes prostate cancer cells to tumor necrosis factor-related apoptosis-inducing ligand/Apo2L by inhibiting nuclear factor-kappaB through suppression of ikappabalpha phosphorylation. Mol Cancer Ther 2004; 3: 803–812.

169.

Holy

. Curcumin inhibits cell motility and alters microfilament organization and function in prostate cancer cells. Cell Motil Cytoskeleton 2004; 58: 253–268.

170.

Dorai

Dutcher

Dempster

, et al. Therapeutic potential of curcumin in prostate cancer–V: interference with the osteomimetic properties of hormone refractory C4-2B prostate cancer cells. Prostate 2004; 60: 1–17.

171.

Chendil

Ranga

Meigooni

, et al. Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3. Oncogene 2004; 23: 1599–1607.

172.

Kumar

Garcia

Ghosh

, et al. 4-Hydroxy-3-methoxybenzoic acid methyl ester: a curcumin derivative targets Akt/NFκB cell survival signaling pathway: potential for prostate cancer management. Neoplasia 2003; 5: 255–266.

173.

Ghosh

. Inhibition of arachidonate 5-lipoxygenase triggers prostate cancer cell death through rapid activation of c-Jun N-terminal kinase. Biochem Biophys Res Commun 2003; 307: 342–349.

174.

Park

Lee

Cho

, et al. Transforming growth factor-beta1 activates interleukin-6 expression in prostate cancer cells through the synergistic collaboration of the Smad2, p38-NF-kappaB, JNK, and ras signaling pathways. Oncogene 2003; 22: 4314–4332.

175.

Chaudhary

Hruska

. Inhibition of cell survival signal protein kinase B/Akt by curcumin in human prostate cancer cells. J Cell Biochem 2003; 89: 1–5.

176.

Deeb

Jiang

, et al. Curcumin (diferuloyl-methane) enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in LNCaP prostate cancer cells. Mol Cancer Ther 2003; 2: 95–103.

177.

Dorai

Gehani

Katz

. Therapeutic potential of curcumin in human prostate cancer-I. curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. Prostate Cancer Prostatic Dis 2000; 3: 84–93.

178.

Mukhopadhyay

Banerjee

Stafford

, et al. Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation. Oncogene 2002; 21: 8852–8861.

179.

Nakamura

Yasunaga

Segawa

, et al. Curcumin down-regulates AR gene expression and activation in prostate cancer cell lines. Int J Oncol 2002; 21: 825–830.

180.

Hour

Chen

Huang

, et al. Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21WAF1/CIP1 and C/EBP? Expressions and suppressing NF-?B activation. Prostate 2002; 51: 211–218.

181.

Mukhopadhyay

Bueso-Ramos

Chatterjee

, et al. Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines. Oncogene 2001; 20: 7597–7609.

182.

Dorai

Cao

Dorai

, et al. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate 2001; 47: 293–303.

183.

Imaida

Tamano

Kato

, et al. Lack of chemopreventive effects of lycopene and curcumin on experimental rat prostate carcinogenesis. Carcinogenesis 2001; 22: 467–472.

184.

Dorai

Gehani

Katz

. Therapeutic potential of curcumin in human prostate cancer. II. Curcumin inhibits tyrosine kinase activity of epidermal growth factor receptor and depletes the protein. Mol Urol 2000; 4: 1–6.

185.

Song

Wang

Pan

, et al. Investigating the multi-target pharmacological mechanism of Hedyotis diffusa Willd acting on prostate cancer: a network pharmacology approach. Biomolecules 2019; 9: 591.

186.

Zhou

, et al. Ursolic acid activates the apoptosis of prostate cancer via ROCK/PTEN mediated mitochondrial translocation of cofilin-1. Oncol Lett 2018; 15: 3202–3206.

187.

Wang

Shu

Zhang

, et al. Histone methyltransferase setd7 regulates nrf2 signaling pathway by phenethyl isothiocyanate and ursolic acid in human prostate cancer cells. Mol Nutr Food Res 2018; 62: e1700840.

188.

Gai

Wang

, et al. Anti-cancer effect of ursolic acid activates apoptosis through ROCK/PTEN mediated mitochondrial translocation of cofilin-1 in prostate cancer. Oncol Lett 2016; 12: 2880–2885.

189.

Pedada

Yarla

Tambade

, et al. Synthesis of new secretory phospholipase a2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents. Eur J Med Chem 2016; 112: 289–297.

190.

Meng

Lin

, et al. Ursolic acid induces apoptosis of prostate cancer cells via the PI3K/Akt/mTOR pathway. Am J Chin Med 2015; 43: 1471–1486.

191.

Mallavadhania

Pattnaik

Suri

, et al. Novel C-ring analogs of ursolic acid: synthesis and cytotoxic evaluation. Nat Prod Commun 2014; 9: 1687–1690.

192.

Kim

Quan

Kim

, et al. Inhibition of estrogen signaling through depletion of estrogen receptor alpha by ursolic acid and betulinic acid from Prunella vulgaris var. lilacina. Biochem Biophys Res Commun 2014; 451: 282–287.

193.

Park

Kwon

Sohn

, et al. Inhibition of wnt/β-catenin signaling mediates ursolic acid-induced apoptosis in PC-3 prostate cancer cells. Pharmacol Rep 2013; 65: 1366–1374.

194.

Shin

Park

. Ursolic acid sensitizes prostate cancer cells to TRAIL-mediated apoptosis. Biochim Biophys Acta 2013; 1833: 723–730.

195.

Limami

Pinon

Leger

, et al. The P2Y2/Src/p38/COX-2 pathway is involved in the resistance to ursolic acid-induced apoptosis in colorectal and prostate cancer cells. Biochimie 2012; 94: 1754–1763.

196.

Liu

Cheng

Liaw

, et al. Bioactive diterpenes from Callicarpa longissima. J Nat Prod 2012; 75: 689–693.

197.

Shanmugam

Ong

Kumar

, et al. Ursolic acid inhibits the initiation, progression of prostate cancer and prolongs the survival of TRAMP mice by modulating pro-inflammatory pathways. PLoS One 2012; 7: e32476.

198.

Koh

Tak

Kim

, et al. Sensitization of ionizing radiation-induced apoptosis by ursolic acid. Free Radic Res 2012; 46: 339–345.

199.

Shin

Kim

Park

. Autophagy inhibition enhances ursolic acid-induced apoptosis in PC3 cells. Biochim Biophys Acta 2012; 1823: 451–457.

200.

Shanmugam

Manu

Ong

, et al. Inhibition of CXCR4/CXCL12 signaling axis by ursolic acid leads to suppression of metastasis in transgenic adenocarcinoma of mouse prostate model. Int J Cancer 2011; 129: 1552–1563.

201.

Shanmugam

Rajendran

, et al. Ursolic acid inhibits multiple cell survival pathways leading to suppression of growth of prostate cancer xenograft in nude mice. J Mol Med 2011; 89: 713–727.

202.

Kondo

MacKinnon

Craft

, et al. Ursolic acid and its esters: occurrence in cranberries and otherVacciniumfruit and effects on matrix metalloproteinase activity in DU145 prostate tumor cells. J Sci Food Agric 2011; 91: 789–796.

203.

Kwon

Park

Kim

, et al. Apoptotic action of ursolic acid isolated from Corni fructus in RC-58T/h/SA#4 primary human prostate cancer cells. Bioorg Med Chem Lett 2010; 20: 6435–6438.

204.

Zhang

Kong

Zeng

, et al. Ursolic acid induces PC-3 cell apoptosis via activation of JNK and inhibition of akt pathways in vitro. Mol Carcinog 2010; 49: 374–385.

205.

Zhang

Kong

Wang

, et al. Ursolic acid overcomes bcl-2-mediated resistance to apoptosis in prostate cancer cells involving activation of JNK-induced bcl-2 phosphorylation and degradation. J Cell Biochem 2010; 109: 764–773.

206.

Zhang

Kong

Wang

, et al. Phosphorylation of Bcl-2 and activation of caspase-3 via the c-Jun N-terminal kinase pathway in ursolic acid-induced DU145 cells apoptosis. Biochimie 2009; 91: 1173–1179.

207.

Kassi

Papoutsi

Pratsinis

, et al. Ursolic acid, a naturally occurring triterpenoid, demonstrates anticancer activity on human prostate cancer cells. J Cancer Res Clin Oncol 2007; 133: 493–500.

208.

Qian

Tao

, et al. Delivery of curcumin nanoliposomes using surface modified with CD133 aptamers for prostate cancer. Drug Des Devel Ther 2019; 13: 4021–4033.

209.

Jahanshahi

Kowsari

Haddadi-Asl

, et al. Sericin grafted multifunctional curcumin loaded fluorinated graphene oxide nanomedicines with charge switching properties for effective cancer cell targeting. Int J Pharm 2019; 572: 118791.

210.

Zhang

Hao

, et al. Enhancement of curcumin antitumor efficacy and further photothermal ablation of tumor growth by single-walled carbon nanotubes delivery system in vivo. Drug Deliv 2019; 26: 1017–1026.

211.

Gracia

Mancini

Colapietro

, et al. Impregnation of curcumin into a biodegradable (poly-lactic-co-glycolic acid, PLGA) support, to transfer its well known in vitro effect to an in vivo prostate cancer model. Nutrients 2019; 11: 2312.

212.

Puiggalí-Jou

Del Valle

Alemán

. Cell responses to electrical pulse stimulation for anticancer drug release. Materials 2019; 12: 2633.

213.

Chu

Tsai

, et al. Correction to codelivery of natural compounds with a dual-targeted nanoparticle delivery system for improving synergistic therapy in an orthotopic tumor model. ACS Appl Mater Interfaces 2020; 12: 19244–19292.

214.

Tang

Mao

. Effective encapsulation of curcumin in nanoparticles enabled by hydrogen bonding using flash nanocomplexation. Int J Pharm 2019; 564: 273–280.

215.

Bessone

Argenziano

Grillo

, et al. Low-dose curcuminoid-loaded in dextran nanobubbles can prevent metastatic spreading in prostate cancer cells. Nanotechnol 2019; 30: 214004.

216.

O'Connor

Einbond

Redenti

, et al. A self-degradable curcumin polymer with anti-cancer activity. J Appl Polym Sci 2018; 135: 46867.

217.

Meng

Cui

Song

, et al. 3D-QSAR and molecular docking studies on design anti-prostate cancer curcumin analogues. Curr Comput Aided Drug Des 2020; 16: 245–256.

218.

Patanapongpibul

Zhang

Chen

, et al. Optimization of diarylpentadienones as chemotherapeutics for prostate cancer. Bioorg Med Chem 2018; 26: 4751–4760.

219.

Gdowski

Johnson

Shah

, et al. Optimization and scale up of microfluidic nanolipomer production method for preclinical and potential clinical trials. Nanobiotechnology 2018; 16: 12.

220.

Cheng

Chou

Wang

, et al. Androgen receptor (AR) degradation enhancer ASC-J9 ® in an FDA-approved formulated solution suppresses castration resistant prostate cancer cell growth. Cancer Lett 2018; 417: 182–191.

221.

Azandeh

Abbaspour

Khodadadi

, et al. Anticancer activity of curcumin-loaded PLGA nanoparticles on PC3 prostate cancer cells. Iran J Pharm Res 2017; 16: 868–879.

222.

Zhang

Guo

Chen

, et al. Asymmetric 1,5-diarylpenta-1,4-dien-3-ones: antiproliferative activity in prostate epithelial cell models and pharmacokinetic studies. Eur J Med Chem 2017; 137: 263–279.

223.

Guan

Zhou

Zhang

, et al. Therapeutic effects of curcumin nanoemulsions on prostate cancer. J Huazhong Univ Sci Technol Med Sci 2017; 37: 371–378.

224.

Saralkar

Dash

. Alginate nanoparticles containing curcumin and resveratrol: preparation, characterization, and in vitro evaluation against DU145 prostate cancer cell line. AAPS PharmSciTech 2017; 18: 2814–2823.

225.

Yan

Wang

Jia

, et al. Co-delivery of docetaxel and curcumin prodrug via dual-targeted nanoparticles with synergistic antitumor activity against prostate cancer. Biomed Pharmacother 2017; 88: 374–383.

226.

Klippstein

Bansal

Al-Jamal

. Doxorubicin enhances curcumin's cytotoxicity in human prostate cancer cells in vitro by enhancing its cellular uptake. Int J Pharm 2016; 514: 169–175.

227.

Aldahoun

Jaafar

Al-Akhras

, et al. Enhanced nanocurcumin toxicity against (PC3) tumor and microbial by using magnetic field in vitro. Artif Cells Nanomed Biotechnol 2017; 45: 843–853.

228.

de Oliveira

Bouchmella

Gonçalves Kde

, et al. Functionalized silica nanoparticles as an alternative platform for targeted drug-delivery of water insoluble drugs. Langmuir 2016; 32: 3217–3225.

229.

Adahoun

Al-Akhras

Jaafar

, et al. Enhanced anti-cancer and antimicrobial activities of curcumin nanoparticles. Artif Cells Nanomed Biotechnol 2017; 45: 98–107.

230.

Shukla

Mathur

Kumar

, et al. Nanoemulsion based concomitant delivery of curcumin and etoposide: impact on cross talk between prostate cancer cells and osteoblast during metastasis. J Biomed Nanotechnol 2014; 10: 3381–3391.

231.

Wang

Chen

Zhang

, et al. Structure–activity relationship and pharmacokinetic studies of 1,5-diheteroarylpenta-1,4-dien-3-ones: a class of promising curcumin-based anticancer agents. J Med Chem 2015; 58: 4713–4726.

232.

Thangavel

Yoshitomi

Sakharkar

, et al. Redox nanoparticles inhibit curcumin oxidative degradation and enhance its therapeutic effect on prostate cancer. J Control Release 2015; 209: 110–119.

233.

Citalingam

Abas

Lajis

, et al. Anti-proliferative effect and induction of apoptosis in androgen-independent human prostate cancer cells by 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one. Molecules 2015; 20: 3406–3430.

234.

Zhou

Ding

Zhao

, et al. Synthesis and evaluation of curcumin-related compounds containing inden-2-one for their effects on human cancer cells. Biol Pharm Bull 2014; 37: 1977–1981.

235.

Samaan

Zhong

Fernandez

, et al. Design, synthesis, and evaluation of novel heteroaromatic analogs of curcumin as anti-cancer agents. Eur J Med Chem 2014; 75: 123–131.

236.

Rao

Zhang

Poventud-Fuentes

, et al. Thermally responsive nanoparticle-encapsulated curcumin and its combination with mild hyperthermia for enhanced cancer cell destruction. Acta Biomater 2014; 10: 831–842.

237.

Soh

Huang

Lee

, et al. Determination of androgen receptor degradation enhancer ASC-J9(®) in mouse sera and organs with liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal 2014; 88: 117–122.

238.

Boztas

Karakuzu

Galante

, et al. Synergistic interaction of paclitaxel and curcumin with cyclodextrin polymer complexation in human cancer cells. Mol Pharm 2013; 10: 2676–2683.

239.

Salehi

Makhoul

Roy

, et al. Curcumin loaded NIPAAM/VP/PEG-A nanoparticles: physicochemical and chemopreventive properties. J Biomater Sci Polym Ed 2013; 24: 574–588.

240.

Aditya

Shim

Lee

, et al. Curcumin and genistein coloaded nanostructured lipid carriers: in vitro digestion and antiprostate cancer activity. J Agric Food Chem 2013; 61: 1878–1883.

241.

Yallapu

Dobberpuhl

Maher

, et al. Design of curcumin loaded cellulose nanoparticles for prostate cancer. Curr Drug Metab 2012; 13: 120–128.

242.

Rejinold

Muthunarayanan

Chennazhi

, et al. Curcumin loaded fibrinogen nanoparticles for cancer drug delivery. J Biomed Nanotechnol 2011; 7: 521–534.

243.

Agashe

Lagisetty

Sahoo

, et al. Liposome-encapsulated EF24-hpβcd inclusion complex: a preformulation study and biodistribution in a rat model inclusion complex: a preformulation study and biodistribution in a rat model. J Nanopart Res 2011; 13: 2609–2623.

244.

Yallapu

Jaggi

Chauhan

. Poly(β-cyclodextrin)/curcumin self-assembly: a novel approach to improve curcumin delivery and its therapeutic efficacy in prostate cancer cells. Macromol Biosci 2010; 10: 1141–1151.

245.

Yallapu

Jaggi

Chauhan

. Beta-cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells. Colloids Surf B Biointerfaces 2010; 79: 113–125.

246.

Mukerjee

Vishwanatha

. Formulation, characterization and evaluation of curcumin-loaded PLGA nanospheres for cancer therapy. Anticancer Res 2009; 29: 3867–3875.

247.

Fuchs

Pandit

Bhasin

, et al. Structure-activity relationship studies of curcumin analogues. Bioorg Med Chem Lett 2009; 19: 2065–2069.

248.

Thangapazham

Puri

Tele

, et al. Evaluation of a nanotechnology-based carrier for delivery of curcumin in prostate cancer cells. Int J Oncol 2008; 32: 1119–1123.

249.

Abas

Hui

Ahmad

, et al. Biological evaluation of curcumin and related diarylheptanoids. Z Naturforsch C Biosci 2006; 61: 625–631.

250.

Lin

Shi

Nyarko

, et al. Antitumor agents. 250. Design and synthesis of new curcumin analogues as potential anti-prostate cancer agents. J Med Chem 2006; 49: 3963–3972.

251.

Kachadourian

Day

. Flavonoid-induced glutathione depletion: potential implications for cancer treatment. Free Radic Biol Med 2006; 41: 65–76.

252.

Ohtsu

Xiao

Ishida

, et al. Antitumor agents. 217. curcumin analogues as novel androgen receptor antagonists with potential as anti-prostate cancer agents. J Med Chem 2002; 45: 5037–5042.

253.

Caldeira de Araújo Lopes

Vinícius Melo Novais

Salviano Teixeira

, et al. Preparation, physicochemical characterization, and cell viability evaluation of long-circulating and pH-sensitive liposomes containing ursolic acid. Biomed Res Int 2013; 2013: 467147.

254.

Murphy

MacKinnon

Yan

, et al. Identification of triterpene hydroxycinnamates with in vitro antitumor activity from whole cranberry fruit (Vaccinium macrocarpon). J Agric Food Chem 2003; 51: 3541–3545.

255.

Taniguchi

Karin

. NF-κB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol 2018; 18: 309–324.

256.

Suhail

Tarique

Muhammad

, et al. A critical transcription factor NF-κB as a cancer therapeutic target and its inhibitors as cancer treatment options. Curr Med Chem 2021; 28: 4117–4132.

257.

Domińska

Kowalska

Matysiak

, et al. Regulation of mRNA gene expression of members of the NF-κB transcription factor gene family by angiotensin II and relaxin 2 in normal and cancer prostate cell lines. Mol Med Rep 2017; 15: 4352–4359.

258.

Russo

Ravenna

Pellegrini

, et al. Hypoxia and inflammation in prostate cancer progression. Cross-talk with androgen and estrogen receptors and cancer stem cells. Endocr Metab Immune Disord Drug Targets 2016; 16: 235–248.

259.

Staal

Beyaert

. Inflammation and NF-κB signaling in prostate cancer: mechanisms and clinical implications. Cells 2018; 7: 122.

260.

Rosa-Ribeiro

Nishan

Vidal

, et al. Transcription factors involved in prostate gland adaptation to androgen deprivation. PLoS One 2014; 9: e97080.

261.

Jin

Lho

Connelly

, et al. The nuclear factor-kappaB pathway controls the progression of prostate cancer to androgen-independent growth. Cancer Res 2008; 68: 6762–6769.

262.

Ferrucci

McCorkle

Smith

, et al. Factors related to the use of dietary supplements by cancer survivors. J Altern Complement Med 2009; 15: 673–680.

263.

Wallace

. Twenty years of the dietary supplement health and education act–how should dietary supplements be regulated? J Nutr 2015; 145: 1683–1686.

264.

Chen

Zhou

, et al. The PI3K/AKT pathway in the pathogenesis of prostate cancer. Front Biosci 2016; 21: 1084–1091.

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