Cytoskeletal reorganization and cell cycle arrest by 5-Aza-2'-deoxycytidine on 267B1/K-ras human prostate cancer cells

Abstract

The demethylating agent, 5-Aza-2'-deoxycytidine, has crucial value for the epigenetic therapies of cancers. Many studies have reported that 5-Aza-2'-deoxycytidine treatment inhibited Dnmts and induced cell proliferation and apoptosis in tumors for cancer therapies, but their exact in vivo mechanism is required more studies and results. In this study, the results show that the 5-Aza-2'-deoxycytidine inhibits the cell proliferation in dose dependent manner. The cell proliferation is arrested at the inhibitory concentration of 10 µM and the exposure time was 72 h. Also, 5-Aza-2'-deoxycytidine causes cell cycle arrest. Especially, Cyclin-dependent kinases (CDKs) and Cdc25A expression decreased remarkably in treated 267B1/K-ras. Inhibition of DNA methylation, ultimately induce the recovery of tumor suppressor genes. Chimaerin in these genes has GTPase？activating protein (GAP) domain that targets Rac and is known to inhibiting expression of Rac. Through the experiment, it is confirmed that increased expression of Chimaerin by 5-Aza-2'-deoxycytidine down-regulates Rac-dependent cytoskeletal pathway on 267B1/K-ras cells. These results represent that 5-Aza-2'-deoxycytidine causes the cell cycle arrest and regulates indirectly Rac-dependent actin polymerization of 267B1/K-ras cells. Therefore it would be appropriate candidate as potent anti-cancer drug.