Procaine Inhibiting Human Bladder Cancer Cell Proliferation by Inducing Apoptosis and Demethylating APAF1 CpG Island Hypermethylated  

作　　者：SUN Ran CHANG Li-ping WANG Kai-chen SUN Hong-yan CONG Xian-ling 

机构地区：[1]Tissue Bank, China-Japan Union Hospital, Jilin University, Changchun 130033, P. R. China, [2]Department of Cardiopathy, the Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, P. R. China [3]Department of Urinary Surgery [4]Department of Dermatology, China-Japan Union Hospital, Jilin University, Changchun 130033, P. R. China

出　　处：《Chemical Research in Chinese Universities》2012年第6期1017-1021,共5页高等学校化学研究（英文版）

基　　金：Supported by the National Natural Science Foundation of China(Nos.81001298,81241093);the Project of China Postdoctoral Science Foundation(No.20100481058);the High-tech Industrial Development Project of Jilin Province,China(No.20090633);the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.20100061120028);the Scientific Research Foundation of Jilin Province,China(Nos.20080739,200905169)

摘　　要：Studies have shown that aberrant DNA methylation of apoptotic protease activating factor-1（APAF1） is an important epigenetic mechanism of gene regulation in the progression of bladder cancer.In this article,we have proved that procaine,an inhibitor of DNA methyltransferases,could inhibit the proliferation of T24 and 5637 human bladder cancer cells by inducing their apoptosis.The mechanism studies reveal that procaine could induce demethylation of APAF1 gene in T24 or 5637 cells,subsequently activating caspase-3/9.It was also shown that the serum soluble fas ligand（sFasL） was activated,and the expression of matrix metallopeptidase 9（MMP-9） was down-regulated.Procaine seems to induce cell death by different pathways,and it might be used as a potential agent for bladder cancer treatment.Studies have shown that aberrant DNA methylation of apoptotic protease activating factor-1（APAF1） is an important epigenetic mechanism of gene regulation in the progression of bladder cancer.In this article,we have proved that procaine,an inhibitor of DNA methyltransferases,could inhibit the proliferation of T24 and 5637 human bladder cancer cells by inducing their apoptosis.The mechanism studies reveal that procaine could induce demethylation of APAF1 gene in T24 or 5637 cells,subsequently activating caspase-3/9.It was also shown that the serum soluble fas ligand（sFasL） was activated,and the expression of matrix metallopeptidase 9（MMP-9） was down-regulated.Procaine seems to induce cell death by different pathways,and it might be used as a potential agent for bladder cancer treatment.

关 键 词：Bladder cancer cell EPIGENETICS DNA methylation Apoptotic protease activating factor-1（APAF1） PROCAINE 

分 类 号：Q253[生物学—细胞生物学] TS27[轻工技术与工程—农产品加工及贮藏工程]