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

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.