Exp Clin Endocrinol Diabetes 2013; 121 - OP5_32a
DOI: 10.1055/s-0033-1336640

The phytoestrogen Genistein inhibits the anti-tumor activity of cisplatin in MCF-7 breast and HT29 colon cancer cells

H Xiao Juan 1, 2, M Xie 2, P Diel 1
  • 1German Sport University Cologne, Department of Molecular and Cellular Sports Medicine, Cologne, Germany
  • 2Nanchang University, State Key Laboratory of Food Science and Technology, Nanchang, China

The function of phytoestrogens, especially Genistein (GEN) in tumor prevention and tumor promotion is controversially discussed but has been investigated in numerous studies. In contrast the interference of genistein with cytostatic drugs during cancer therapy has been only rarely addressed so far. In this study, effects of GEN on the anti-tumor activity of cisplatin (CIS), were investigated in the presence and absence of estradiol (E2) in MCF-7 breast and HT29 colon cancer cells. MCF-7 and HT 29 cell were dose dependently treated with GEN, E2, CIS and combinations. Cell viability assays, cell cycle analysis by flowcytometry and M30 immuno-fluorescence staining were used to determine cell growth, proliferation and apoptosis. To further investigate molecular mechanisms, biomarkers such as PCNA, Ki67 and BAX/BCL2 were measured by western blot and/or real-time PCR.

In a concentration of 10-4 M CIS and GEN, in the presence and absence of E2, inhibit cell growth and induce apoptosis in MCF-7 and in HT 29 cells. Co-treatment with 10-4 M CIS and GEN results in additive effects. In contrast in doses of 10-5 and 10-6 M, GEN increases growth of MCF-7 cells. It stimulates proliferation and inhibits apoptosis. Remarkably in these concentrations it also counteracts the anti-tumor activity of CIS in MCF-7 but also HT-29 cells. Especially the ability of CIS to induce apoptosis was antagonized. In ER alpha positive MCF-7 cells, but not in ER alpha negative HT 29 cells E2 was able to neutralize the effects of GEN on CIS activity.

Our data provide evidence, that GEN in the absence of E2, a situation which occurs in postmenopausal woman, directly affects the antitumor activity of cytostatic drugs like cisplatin. The exact molecular mechanism has to be investigated in future studies. In exposure scenarios were tumor patients may uptake isoflavones by diet this observation is of specific relevance.