Red clover and soy isoflavones--an in vitro safety assessment.

Isoflavones from red clover and soy plant extracts are used in highly concentrated food supplements as an alternative to hormone replacement therapy. Due to their estrogenic activity, isoflavones are a focus of safety concerns about their potential to promote the growth of hormone-dependent cancer cells. In this study, isoflavones and plant extracts were tested for their effect on cell proliferation, apoptosis induction and cell cycle arrest. Isoflavones and plant extracts were applied in proliferation assays on 11 human cancer cell lines (representing cancers of the colon, prostate, breast, cervix, liver, pancreas, stomach and ovaries) and a fibroblast line to detect cytotoxic activity. Fluorescence-activated cell sorting was used to detect the induction of apoptosis or cell cycle arrest. Isoflavones and plant extracts significantly reduced the proliferation activity of the treated cancer cell lines. Growth promotion was not observed, but apoptosis or necrosis induction was, as was cell cycle arrest, with genistein as the most potent isoflavone. Isoflavones and plant extracts from soy and red clover, respectively, do not promote the growth of human cancer cells but induce decreased cell proliferation, increased apoptosis and cell cycle arrest. These results indicate that isoflavones can be considered safe compounds.