Genistein inhibits tamoxifen effects on cell proliferation and cell cycle arrest in T47D breast cancer cells.
Tamoxifen is an antiestrogen used in the treatment of estrogen receptor-positive breast cancer in postmenopausal women. It functions by competitively inhibiting the estrogen receptor and inducing apoptosis and G1 cell cycle arrest. Genistein is a soy phytoestrogen that inhibits breast cancer cell growth in vitro at doses of 10 microM or above. At lower doses genistein may stimulate cell growth and entry into the cell cycle. We hypothesized that treatment with low-dose genistein would reverse the inhibitory effects of tamoxifen in estrogen-receptor-positive breast cancer cells. Cell cycle kinetics and cell proliferation in T47-D human breast cancer cells were examined after exposure to genistein and tamoxifen in a low-estrogen environment designed to mimic a post-menopausal state. Cell proliferation was assessed by a colorimetric assay. Cell cycle kinetics were determined by flow cytometry. Tamoxifen caused G1 arrest and a decrease in proliferation. Genistein reversed the inhibitory effects of tamoxifen on both proliferation and G1 arrest. Thus low-dose genistein was able to inhibit the therapeutic effects of tamoxifen in this postmenopausal model of breast cancer.
Jones
Julie L
JL
Department of Surgery, University of Tennessee Medical Center, Knoxville 37920-6999, USA.
Daley
Brian J
BJ
Enderson
Blaine L
BL
Zhou
Jin-Rong
JR
Karlstad
Michael D
MD
D000970:Antineoplastic Agents / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000037:antagonists & inhibitors*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D006131:Growth Inhibitors; D011960:Receptors, Estrogen; D013629:Tamoxifen; D019833:Genistein