Cucurbitacin B and Its Rapidly Emerging Role in the Management of Systemic Malignancies Besides Lung Carcinomas

Dear editor:

The recent article by Lu et al. was highly thought provoking. ¹ Cucurbitacin B is a significant potentiator of tumor growth inhibition in a number of systemic malignancies besides lung carcinomas.

Cucurbitacin B attenuates MMP-9 expression and inactivates the PI3K/Akt signal transduction pathways thereby decreasing the metastatic potential of hepatocellular carcinomas. ² Cucurbitacin B also accentuates transcription-3 signaling in pancreatic malignancies thereby attenuating tumor growth in these cancers. ³ Cucurbitacin B also enhances the apoptotic properties of chemotherapeutic agents, such as gemcitabine, and thereby has a significant role to play in the treatment of pancreatic malignancies. ⁴ Sensitivity to chemotherapeutic agents, such as cisplatin, is also potentiated in laryngeal squamous cell carcinomas following the coadministration of cucurbitacin B. ⁵

Cucurbitacin B exhibits antineoplastic properties in malignant melanomas by initiating a decrease in the G-actin pool via reactive oxygen species -dependent actin aggregation. ⁶ Interestingly, the sensitivity of malignant melanoma cells to cucurbitacin B administration is potentiated by the coadministration of histone deacetylase inhibitors, such as valproic acid. ⁷ Antineoplastic effects secondary to cucurbitacin B administration are also observed in skin squamous cell carcinomas. ⁸

Cucurbitacin B inhibits the JAK/STAT3 pathway and activates the JNK pathway thereby accentuating cellular apoptosis in B cell leukemias. ⁹ Similarly, significant anti-neoplastic effects are noticed in bone tumors, such as osteosarcomas, following cucurbitacin B administration. In fact, cucurbitacin B exhibits synergetic effects when coadministered with methotrexate in osteosarcomas. ¹⁰

The above examples clearly illustrate the significant antiproliferative effects of cucurbitacin B. The above examples highlight the potential use of cucurbitacin B for attenuating growth in malignancies ranging from hepatocellular carcinomas to osteosarcomas and the need for further studies to fully elaborate its antineoplastic potential.