Plant Estrogens: Effects on Cell Cycle Progression in Breast Cancer Cells
Annual rept. 1 Jun 1999-31 May 2000
UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
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Epidemiological evidence and studies in cancer models suggest that dietary plant estrogens phytoestrogens reduce the risk of breast cancer. In this work we examined the role of phytoestrogens as anti-cancer drugs by inhibiting cell proliferation through mechanisms independent of the tumour suppressor p53. This is relevant since p53 is found mutated or absent in half of the human tumors. Using p53-deficient breast cancer cell lines BT2O and T47D, we studied the anti-proliferative effects and the mechanism of action of several phytoestrogens biochanin, daidzein, genistein, and genistin. The main finding were genistein and genistin seem to posses anticancer drug characteristics as suggested by inhibition of cell proliferation and cell cycle arrest G2 arrest occurred upon treatment with phytoestrogens cells were G2 arrested with no p21 expression increase, thereby suggesting a p21-independent pathway for cell cycle arrest Cdc2 activity was decreased by genistein with no changes in p21 expression. The results suggest that phytoestrogens not only have preventive effect, but can also act as anti-breast cancer drugs, by a mechanism that is independent of p53.
- Medicine and Medical Research
- Food, Food Service and Nutrition