title: Genistein modulates the anti-tumor activity of cisplatin in MCF-7 breast and HT-29 colon cancer cells.
abstract: The function of genistein (GEN) on tumor prevention and tumor promotion is discussed controversially. A possible interference of GEN with chemotherapy 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 (10(-10) M) in MCF-7 breast and HT-29 colon cancer cells. Cells were treated with graded concentrations of GEN (10(-4)-10(-6) M), E2, CIS and combinations. Cell growth, proliferation and apoptosis were determined as well as the expression level of PCNA, Ki67 and BCL-2 family members. CIS and GEN 10(-4) M inhibited cell growth and induced apoptosis in MCF-7 and HT-29 cells in the presence and absence of E2. Co-treatment with CIS and 10(-4)M GEN resulted in additive effects. In concentrations of 10(-5) and 10(-6) M, GEN stimulated cell growth in MCF-7 cells. It promoted proliferation, inhibited apoptosis and counteracted the anti-tumor activity of CIS in MCF-7 and HT-29 cells. Particularly 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 anti-CIS effects of GEN. Our data provide evidence that GEN in the absence of E2, a situation which occurs in postmenopausal women, directly affects the anti-tumor activity of cytostatic drugs like CIS. The exact molecular mechanism has to be investigated in future studies.
authors: Department of Cellular and Molecular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sports University Cologne, Am Sportpark Muengersdorf 6, 50933, Koeln, Germany.
authors: Xiao-Juan
authors: XJ
authors: Hu
authors: Ming-Yong
authors: MY
authors: Xie
authors: Felix M
authors: FM
authors: Kluxen
authors: Patrick
authors: P
authors: Diel
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D019073:HT29 Cells / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004958:Estradiol; D019833:Genistein; D002945:Cisplatin