Genistein, an isoflavone in soybean products, has been reported to influence many biological processes,
of which suppression of cell proliferation and stimulation of apoptosis are considered to be the major
pathways underlying its inhibition of tumorigenesis. In this study, we investigated the effect of genistein
on apoptosis of AGS human gastric carcinoma and SK-MEL-2 melanoma cells. Genistein treatment
resulted in the inhibition of cell proliferation in a concentration-dependent manner. The anti-proliferative
effect of genistein was associated with formation of apoptotic bodies, and flow cytometry analysis confirmed
that genistein treatment increased populations of apoptotic-sub G1 phase. Apoptotic cell death by
genistein was connected with a down-regulation of anti-apoptotic Bcl-2 expression and an up-regulation
of pro-apoptotic Bax expression. Genistein induced the proteolytic activation of caspase-3 and down-regulation
of inhibition of apoptosis protein (IAP) family expression, and a concomitant degradation of poly
(ADP-ribose) polymerase (PARP) and phospholipas C-γ1 (PLCγ1). Pretreatment of AGS and SK-MEL-2
cells with the selective caspase-3 inhibitor z-DEVD-fmk significantly blocked the genistein- induced
apoptosis. These data confirmed that genistein-induced apoptosis is mediated through activation of caspase-
3-dependent pathway. Taken together, these findings partially provide novel insights into the possible
molecular mechanism of the anti-cancer activity of genistein.

Keywords: Genistein, AGS, SK-MEL-2, Apoptosis, Caspase-3