Biphasic effects of kaempferol on the estrogenicity in human breast cancer cells

Dietary flavonoids have attracted a great deal of attention as agents for preventing estrogen-related diseases, such as postmenopausal symptoms, and for reducing the risk of estrogen-dependent cancer. Kaempferol is one of the most commonly found dietary phytoestrogen. The aim of this study was to investigate the estrogenic and/or antiestrogenic effect of kaempferol, which can confirm its potency as a preventive agent against estrogen-related diseases. Kaempferol has both estrogenic and antiestrogenic activity, which are biphasic response on estrogen receptor. The estrogenic activity of kaempferol induced via ER-mediated pathway depending on E-2 concentration (<= 10(-12) M). Kaempferol (10(-5) M) also caused antiproliferative effect on MCF-7 cell in the presence of E-2 (10(-11) M) and restored to the addition of excess E-2 (10(-7) M), which confirms that antiproliferation of kaempferol was induced via ER-dependent pathway. However, at 10(-4) M, concentration higher than the concentrations at which the estrogenic effects of kaempferol are detected (10(-5) M), kaempferol induced strong antiproliferative effect, but were unaffected by the addition of excess E-2 (10(-7) M) indicating that kaempferol exerts antiproliferation via ER-independent pathway. In particular, kaempferol blocked the focus formation induced by E-2, which confirms that kaempferol might inhibit the malignant transformation caused by estrogens. Therefore, we suggested that kaempferol might regulate a suitable level of estrogenic activity in the body and is expected to have potential beneficial effects in preventing estrogen imbalance diseases (breast cancer, osteoporosis, cardiovascular disease and etc.).