Soy isoflavones suppress invasiveness of breast cancer cells by the inhibition of NF-κB/AP-1-dependent and -independent pathways

High consumption of soy products in some Asian countries has been linked to the low incidence of breast cancer in women. The chemopreventive effect of the soy isoflavone, genistein, has been observed through the suppression of cell proliferation, inhibition of angiogenesis and stimulation of apoptosis in breast carcinoma cells. Cancer metastasis consists of interdependent processes, including cell adhesion, migration and invasion. In the present study, we compare the effect of soy isoflavones in the form of aglycones (genistein, daidzein and glycitein) and glucosides (genistin, daidzin and glycitin) on the behavior of highly invasive breast cancer cells. Here we demonstrate that genistein suppresses cell adhesion and migration by inhibiting the constitutively active transcription factors NF-kappaB and AP-1, resulting in the suppression of secretion of urokinase-type plasminogen activator (uPA) in breast cancer cells MDA-MB-231. In addition, we show that all tested soy isoflavone aglycones (genistein, daidzein, glycitein) and glucosides (genistin, daidzin, glycitin) markedly reduced motility of MDA-MB-231 cells. However, only genistein and daidzein inhibited constitutively active NF-kappaB and AP-1 and suppressed secretion of uPA from breast cancer cells. Taken together, our results suggest that dietary soy isoflavones inhibit adhesion and motility of highly invasive breast cancer cells by distinct signaling pathways.