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Genistein‐induced mitotic arrest of gastric cancer cells by downregulating KIF 20 A , a proteomics study
Author(s) -
Yan GuangRong,
Zou FeiYan,
Dang BianLi,
Zhang Ye,
Yu Guangchuang,
Liu Xiao,
He QingYu
Publication year - 2012
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201100652
Subject(s) - genistein , cancer , cancer cell , chemistry , viability assay , proteomics , apoptosis , biology , microbiology and biotechnology , cancer research , biochemistry , genetics , gene
Genistein exerts its anticarcinogenic effects by inducing G 2/ M arrest and apoptosis of cancer cells. However, the precise molecular mechanism of action of genistein has not been completely elucidated. In this study, we used quantitative proteomics to identify the genistein‐induced protein alterations in gastric cancer cells and investigate the molecular mechanism responsible for the anti‐cancer actions of genistein. Total 86 proteins were identified to be regulated by genistein, most of which were clustered into the regulation of cell division and G 2/ M transition, consistent with the anti‐cancer effect of genistein. Many proteins including kinesin family proteins, TPX 2, CDCA 8, and CIT were identified for the first time to be regulated by genistein. Interestingly, five kinesin family proteins including KIF 11, KIF 20 A , KIF 22, KIF 23, and CENPF were found to be simultaneously downregulated by genistein. Significantly decreased KIF 20 A was selected for further functional studies. The silencing of KIF 20 A inhibited cell viability and induced G 2/ M arrest, similar to the effects of genistein treatment in gastric cancer. And the silencing of KIF 20 A also increased cancer cell sensitivity to genistein inhibition, whereas overexpression of KIF 20 A markedly attenuated genistein‐induced cell viability inhibition and G 2/ M arrest. These observations suggested that KIF 20 A played an important role in anti‐cancer actions of genistein, and thus may be a potential molecular target for drug intervention of gastric cancer.