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 ...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.展开更多
The protein apoptoUc protease activating factor I （Apafl） is the central component of the apoptosome, a multiprotein complex that activates procaspase-9 after cytochrome c release from the mitochondria in the intrin...The protein apoptoUc protease activating factor I （Apafl） is the central component of the apoptosome, a multiprotein complex that activates procaspase-9 after cytochrome c release from the mitochondria in the intrinsic pathway of apoptosis. We have developed a vital method that allows fluorescence-activated cell sorting of cells at different stages of the apoptotic pathway and demonstrated that upon pharmacological inhibition of Apafl, cells recover from doxorubicinor hypoxia-induced early apoptosis to normal healthy cell. Inhibiting Apafl not only prevents procaspase-9 activation but delays massive mitochondrial damage allowing cell recovery.展开更多
基金Supported by the National Natural Science Foundation of China(Nos.81001298,81241093)the Project of China Postdoctoral Science Foundation(No.20100481058)+2 种基金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)
文摘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.
文摘The protein apoptoUc protease activating factor I （Apafl） is the central component of the apoptosome, a multiprotein complex that activates procaspase-9 after cytochrome c release from the mitochondria in the intrinsic pathway of apoptosis. We have developed a vital method that allows fluorescence-activated cell sorting of cells at different stages of the apoptotic pathway and demonstrated that upon pharmacological inhibition of Apafl, cells recover from doxorubicinor hypoxia-induced early apoptosis to normal healthy cell. Inhibiting Apafl not only prevents procaspase-9 activation but delays massive mitochondrial damage allowing cell recovery.
