|
KMID : 1140120060110030225
|
|
Cancer Prevention Research
2006 Volume.11 No. 3 p.225 ~ p.234
|
|
|
Induction of Apoptosis by Genistein through Caspase-3 Activation in Human Gastric Carcinoma and Melanoma Cells
|
|
Kim Jung-Im
Park Cheol
Choi Byung-Tae
Rhu Chung-Ho
Lee Won-Ho
Choi Yung-Hyun
|
|
|
Abstract
|
|
|
|
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.
|
|
|
KEYWORD
|
|
|
Genistein, AGS, SK-MEL-2, Apoptosis, Caspase-3
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
 
|