Comparative Studies of Steroidogenesis Inhibitors (Econazole,Ketoconazole) on Human Breast Cancer MCF-7 Cell Proliferation by Growth Experiments,Thymidine Incorporation and Flow Cytometric DNA Analysis
Restricted accessResearch articleFirst published online October, 1991
Comparative Studies of Steroidogenesis Inhibitors (Econazole,Ketoconazole) on Human Breast Cancer MCF-7 Cell Proliferation by Growth Experiments,Thymidine Incorporation and Flow Cytometric DNA Analysis
The effects of aminoglutethlmide, econazole and ketoconazole on human breast cancer cells In culture were compared with those of tamoxifen using four methods (growth experiments, thymidine incorporation, monoparameter and bivariate DNA content flow cytometry analysis). Aminoglutethlmide (1 nM-10 μM) had no effect on cell proliferation after 8 days of treatment and did not decrease thymidine tritiated incorporation during logarithmic phase. Even at 20 μM, similar results were obtained with flow cytometry. Econazole and ketoconazole (1 nM-1 μM) decreased MCF-7 cell proliferation in a time- and dose- dependent fashion. They also decreased tritiated thymidine incorporation. By using flow cytometry and a monoclonal antibody against bromodeoxyuridine, we showed an accumulation of MCF-7 cells treated by imidazoles derivatives In G0-G1 phase of the cell cycle.
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References
1.
AaboK., KjaerM., HansenH.H.: High-dose ketoconazole to untreated stage D prostate cancer.Eur. J. Cancer Clin. Oncol., 24: 431–435, 1988.
2.
Abul-HajjY.J.: Inhibition of androgen aromatization in human breast cancer.J. Steroid Biochem., 13: 1395–1400, 1980.
3.
BruningP.F., BonfrerJ.M.G., HartA.A.M., Van Der LindenE., De Jong-BakkerM., MoolenaarA.J., NooijenW.J.: Low dose aminoglutethimide without hydrocortisone for the treatment of advanced postmenopausal breast cancer.Eur. J. Cancer Clin. Oncol., 25: 369–374, 1989.
4.
BrunkC.F., JonesK.C., JamesT.W.: Assay for nanogram quantities of DNA in cellular homogenates.Anal. Biochem., 29: 369–376, 1979.
5.
ChaudharyL.R., StoccoD.M.: Inhibition of hCG- and cAMP-stimulated progesterone production in MA-10 mouse Leydig tumor cells by ketoconazole.Biochemistry International, 18: 251–256, 1989.
6.
DeanP.N., JettJ.H.: Mathematical analysis of DNA distributions derived from flow microfluorometry.J. Cell Biol., 60: 523–528, 1974.
7.
De FazioA., MusgroveE.A., Tattersall: Flow cytometric enumeration of drug-resistant tumor cells.Cancer Res., 48: 6037–6042, 1988.
8.
DimattinaM., LoriauxD.L., MaronianN., AlbertsonB.D., AshbyH.: Ketokonazole inhibits multiple steroidogenic enzymes involved in androgen biosynthesis in the human ovary.Fertil. Steril., 49: 62–67, 1988.
9.
DolbeareF.A., GratznerH.G., PallaviciniM.G., GrayJ.W.: Flow cytometric measurement of total DNA content and incorporated bromodeoxyuridine.Proc. Natl. Acad. Sci., USA, 80: 5573–5578, 1983.
10.
EngelhardtD., JacobK., DoerrH.G.: Different therapeutic efficacy of ketoconazole in patients with Cushing's syndrome.Klin. Wochenschr., 67: 241–246, 1989.
11.
FranceJ.T., MasonJ.I., MagnessR.R., MurryB.A., RosenfeldC.R.: Ovine placental aromatase: studies of activity levels, kinetics characteristics and effects of aromatase inhibitors.J. Steroid Biochem., 28: 155–160, 1987.
12.
GratznerH.G.: Monoclona antibody to 5-bromo- and 5-iododeoxyuridine: a new reagent for detection of DNA replication.Science, 218: 474–477, 1982.
13.
HarrisA.L., CantwellB.M.J., DowsettM.: High dose ketoconazole: endocrine and therapeutic effects in postmenopausal breast cancer.Br. J. Cancer, 58: 493–498, 1988.
14.
JozanS., KreitmannB., BayardF.: Different effects of estradiol, oestriol, oestetrol and of oestrone on human breast cancer cells (MCF-7) in long term tissue culture.Acta Endocrinol., 98: 73–78, 1981.
15.
NajidA.: Adrenal androgens and mammary cancer.Cah. Cancerol., 3: 612–615, 1991.
16.
NajidA.: Aromatization of DHEA by hormone dependent human mammary cancer MCF-7 subcellular fractions.Eur. J. Cancer, 26: 1001–1002, 1991.
17.
NajidA.: Comparison of DHEA metabolism by MCF-7 cells in culture and by their extracts.Cancer Journal, 4: 45–48, 1991.
18.
NajidA., BeneytoutJ.L., TixierM.: Cytotoxicity of arachidonic acid and of its lipoxygenase metabolite 15-hydroperoxyeicosatetraenoic acid on human breast cancer MCF-7 cells in culture.Cancer Lett., 46: 136–141, 1989.
19.
RestrepoA., StevensD.S., UtxJ.P.: First international symposium on ketoconazole.Rev. Infect. Dis., 2: 519–524, 1980.
20.
RiccardiA., DanovaM., WilsonG., UcciG., DörmerP., MazziniG., BrugnatelliS., GirinoM., McNallyN.J., AscariE.: Cell kinetics in human malignancies studied with in vivo administration of bromodeoxyuridine and flow cytometry.Cancer Res., 48: 6238–6243, 1988.
21.
RochlitzC.F., DamonL.E., RussiM.B., GeddesA., CadmanE.C.: Cytotoxicity of ketoconazole in malignant cell lines.Cancer Chemother. Pharmacol., 21: 319–324, 1988.
22.
RoperP.R., DrewinkoB.: Comparison of in vitro methods to determine drug-induced cell lethality.Cancer Res., 36: 2182–2187, 1976.
23.
SalhanickH.A.: Basic studies on aminoglutethimide.Cancer Res. (Suppl.), 42: 3315s–3320s, 1982.
24.
SouleH.D., VazquezJ., LongA., AlbertS., BrennanM.: A human cell line from a pleural effusion derived from a breast carcinoma.J. Natl. Cancer Inst., 51: 1409–1414, 1973.
25.
VindeløvL.L., ChristensenI.J., NissenN.I.: A detergentrypsin method for the preparation of nuclei for flow cytometric DNA analysis.Cytometry, 3: 323–329, 1983.
26.
VorherH.: Endocrinology of breast cancer.Maturitas, 9: 113–122, 1987.
27.
ZumoffB.: Hormonal profiles in women with breast cancer (Review).Anticancer Res., 8: 627–636, 1988.
