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Li, Yong‐Chao; Wang, Yun; Li, Dan‐Dan; Zhang, Ying; Zhao, Tian‐Cheng; Li, Chang‐Feng
Journal of cellular biochemistry, February 2018, 2018-02-00, 20180201, Letnik: 119, Številka: 2Journal Article
DNA hypermethylation and the silencing of tumor suppressor genes caused by DNA hypermethylation is considered as a molecular hallmark of many kinds of cancers. Procaine, a local anesthetic, has been shown as a potential DNA methylation inhibitor in some types of cancers. However, the influence of procaine on DNA methylation regulation as well as the biological function in gastric cancer is still unknown. We report here that procaine represses the DNA‐methylation level and promotes the proliferation arrest and apoptosis of gastric cancer cells. Global DNA methylation measurement demonstrates that procaine significantly reduces the global DNA methylation level. Analyses of the DNMTs expression and activity show procaine represses the activity, but not the expression, of DNMT1/DNMT3A. Further evidence on specific genes shows that procaine reduces the DNA methylation level in the promoter regions of CDKN2A and RARβ genes through abrogating the binding of DNMT1/DNMT3A toward these regions. This repression would not be reversed by the overexpression of DNMT1/DNMT3A. Moreover, RT‐qPCR and luciferase report assays demonstrate that procaine leads to the upregulation of CDKN2A and RARβ due to the activation of the promoter of these genes. In the end, we test the function of procaine toward gastric cancer cells and find that procaine has the growth inhibitory and apoptosis inducement effect toward gastric cancer cells. Collectively, our data not only uncovers the regulation mechanisms of procaine to DNA methylation but also suggests an anti‐tumor potential of procaine specific to the gastric carcinoma and provides a new therapeutic strategy for gastric carcinoma. In this study, we investigated the influence of procaine on DNA methylation as well as on cell proliferation and apoptosis of gastric cancer cells. We found that procaine repressed the activity but not the expression of DNMT1 and DNMT3A. Further evidence showed that procaine increased the expression of CDKN2A and RARβ through activating the promoter activity of those genes, which is determined by the DNA methylation level. Functionally, procaine inhibited the proliferation and induced the apoptosis of gastric cancer cells. Our results describe a critical role of procaine in the expression of DNMT1 and some critical target genes and suggest the procaine treatment might be a new therapeutic strategy for gastric cancer.
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in: SICRIS
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