Genistein-induced mitotic arrest of gastric cancer cells by downregulating KIF20A, a proteomics study.
Genistein exerts its anticarcinogenic effects by inducing G2/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 G2/M transition, consistent with the anti-cancer effect of genistein. Many proteins including kinesin family proteins, TPX2, CDCA8, and CIT were identified for the first time to be regulated by genistein. Interestingly, five kinesin family proteins including KIF11, KIF20A, KIF22, KIF23, and CENPF were found to be simultaneously downregulated by genistein. Significantly decreased KIF20A was selected for further functional studies. The silencing of KIF20A inhibited cell viability and induced G2/M arrest, similar to the effects of genistein treatment in gastric cancer. And the silencing of KIF20A also increased cancer cell sensitivity to genistein inhibition, whereas overexpression of KIF20A markedly attenuated genistein-induced cell viability inhibition and G2/M arrest. These observations suggested that KIF20A played an important role in anti-cancer actions of genistein, and thus may be a potential molecular target for drug intervention of gastric cancer.
Institute of Life and Health Engineering, and National Engineering and Research Center for Genetic Medicine, Jinan University, Guangzhou, China.
Guang-Rong
GR
Yan
Fei-Yan
FY
Zou
Bian-Li
BL
Dang
Ye
Y
Zhang
Guangchuang
G
Yu
Xiao
X
Liu
Qing-Yu
QY
He
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects*; D060066:Protein Interaction Maps / Q000187:drug effects; D020543:Proteome / Q000032:analysis / Q000187:drug effects*; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D016588:Anticarcinogenic Agents; C410089:KIF20A protein, human; D020543:Proteome; D034741:RNA, Small Interfering; D019833:Genistein; D016547:Kinesins