Genistein, a natural isoflavonoid phytoestrogen, is a strong inhibitor of protein tyrosine kinase and
DNA topoisomerase II activities. Genistein has been shown to have anticancer proliferation, differentiation
and chemopreventive effects. In the present study, we investigated the mechanism of action
by which genistein suppressed the proliferation of AGS human gastric carcinoma and SK-MEL-2
melanoma cells. Treatment of AGS and SK-MEL-2 cells to genistein resulted in the growth inhibition
and morphological change in a dose-dependent manner. Flow cytometric analysis revealed that genistein
treatment caused G2/M phase arrest of the cell cycle, which was associated with a down-regulation of
cyclin A, cyclin B1 and cyclin-dependent kinase (Cdk) 2. And we also observed down-regulation of
Cdc25C, which was a marker of cell proliferation, and plays important role in cyclin B-Cdc2 complex
activation, however Wee1 kinase expression was not affected. Furthermore, genistein induced Cdk
inhibitor p21 (WAF1/CIP1) expression through p53-independent manner in AGS cells, but not affect
in SK-MEL-2 cells. Taken together, these data provide strong molecular evidence for the anti-tumor
activity of genistein in AGS human gastric carcinoma and SK-MEL-2 melanoma cells.

Keywords: Genistein, AGS, SK-MEL-2, G2/M arrest, p21