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	Genistein induces G2/M cell cycle arrest and apoptosis of human ovarian cancer cells via activation of DNA damage checkpoint pathways
	Ouyang, Gaoliang ; 欧阳高亮 ; Yao, Luming ; Ruan, Kai ; Song, Gang ; Song, Gang ; Mao, Yubin ; Bao, Shideng
	2009
关键词	Genistein Apoptosis DNA damage checkpoint Ovarian cancer cell
英文摘要	Genistein is a major isoflavonoid in dietary soybean, commonly consumed in Asia. Genistein exerts inhibitory effects on the proliferation of various cancer cells and plays an important role in cancer prevention. However, the molecular and cellular mechanisms of genistein on human ovarian cancer cells are still little known. We show that exposure of human ovarian cancer HO-8910 cells to genistein induces DNA damage, and triggers G2/M phase arrest and apoptosis. Furthermore, we also found that checkpoint proteins ATM and ATR are phosphorylated and activated in the cells treated with genistein. It is also shown that genistein increases the phosphorylation and activation of Chk1 and Chk2, which results in the phosphorylation and inactivation of phosphatases Cdc25C and Cdc25A, and thereby the phosphorylation and inactivation of Cdc2 which arrests cells in G2/M phase. Moreover, genistein enhances the phosphorylation and activation of p53, while decreases the ratio of Bcl-2/Bax and Bcl-xL/Bax and the level of phosphorylated Akt, which result in cells undergoing apoptosis. These results demonstrate that genistein-activated ATM-Chk2-Cdc25 and ATR-Chk1-Cdc25 DNA damage checkpoint pathways can arrest ovarian cancer cells in G2/M phase, and induce apoptosis while the cellular DNA damage is too serious to be repaired. Thus, the antiproliferative, DNA damage-inducing and pro-apoptotic activities of genistein are probably responsible for its genotoxic effects on human ovarian cancer HO-8910 cells. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.; National Natural Science Foundation of China [30400239, 30570935, 30871242]; Program for New Century Excellent Talents in Xiamen University
语种	英语
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
内容类型	期刊论文
源URL	[http://dx.doi.org/doi:10.1016/j.cellbi.2009.08.011]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Ouyang, Gaoliang,欧阳高亮,Yao, Luming,et al. Genistein induces G2/M cell cycle arrest and apoptosis of human ovarian cancer cells via activation of DNA damage checkpoint pathways[J],2009.
APA	Ouyang, Gaoliang.,欧阳高亮.,Yao, Luming.,Ruan, Kai.,Song, Gang.,...&Bao, Shideng.(2009).Genistein induces G2/M cell cycle arrest and apoptosis of human ovarian cancer cells via activation of DNA damage checkpoint pathways..
MLA	Ouyang, Gaoliang,et al."Genistein induces G2/M cell cycle arrest and apoptosis of human ovarian cancer cells via activation of DNA damage checkpoint pathways".(2009).

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