Regulation of inducible nitric oxide synthase by dietary phytoestrogen in MCF-7 human mammary cancer cells.

We examined the effects of the phytoestrogen biochanin A on the growth of the MCF-7 human breast cancer cell line. The results showed that biochanin A treatment induced dose- and time-dependent inhibition on MCF-7 cell growth at concentrations above 20 microg x mL(-1). An examination of treated MCF-7 cell morphology revealed condensation of the chromosome and dehydration of the cytoplasm, suggesting apoptosis as an important factor in biochanin A-related cell growth inhibition. The results also showed that at a concentration of 40 microg x mL(-1), biochanin A decreased the levels of inducible nitric oxide synthase, thus inhibiting the production of nitric oxide, a known second messenger and inducer of apoptosis, and affecting the overall cell protein pattern. No significant difference in superoxide dismutase protein levels were, however detected at concentrations of 40 or 100 microg x mL(-1) of biochanin A. The data suggest that the inhibitory effects of biochanin A on human breast cancer cell growth are linked to inducible nitric oxide synthase and the associated production of nitric oxide.