KMID : 1140120060110010046
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Cancer Prevention Research 2006 Volume.11 No. 1 p.46 ~ p.57
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Induction of G2/M Arrest of the Cell Cycle and Apoptosis by Genistein in SK-MEL-2 Human Melanoma Cells
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Kim Jung-Im
Park Cheol Choi Woo-Young Lee Jeong-Ok Hong Su-Hyun Hong Sang-Hoon Lee Won-Ho Rhu Chung-Ho Choi Yung-Hyun
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Abstract
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Genistein, a soy metabolite, is a potential chemopreventive agent against various types of cancer. There are several studies documenting molecular alterations leading to cell cycle arrest and induction of apoptosis in a variety of cancer cell lines; however, its mechanism of action and its molecular targets on human melanoma cells remain unclear. In this study, we monitored that genistein inhibited the cell growth in SK-MEL-2 human melanoma cells. It was found that genistein inhibits cell growth in a dose- dependent manner, which was associated with dendrite-like morphological change and apoptotic cell death. Flow cytometry analysis showed that genistein could cause an arrest at the G2/M phase of the cell cycle, which was associated with a down-regulation of cyclin-dependent kinase (Cdk2) and Cdc2 phosphorylation However, genistein did not affect the levels of Cdk inhibitor p21 (WAF1/CIP1) and tumor suppressor p53 in SK-MEL-2 cells. The induction of apoptotic cell death by genistein was associated with a down-regulation of anti-apoptotic Bid and an inhibition of apoptosis proteins (IAPs) family expression, and up-regulation of Fas and FasL protein. Genistein treatment also induced the proteolytic activation of caspase-3 and a concomitant inhibition and/or degradation of poly (ADP-ribose) polymerase (PARP), phospholipas C-¥ã1 (PLC¥ã1) and ¥â-catenin. The present results suggest that genistein has divergent biological function, additional studies will be needed to evaluate the molecular mechanisms of the interaction between genistein and other agents.
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KEYWORD
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Genistein, SK-MEL-2, Cell cycle, Apoptosis
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