Procaine is a specific DNA methylation inhibitor with anti‐tumor effect for human gastric cancer
| Autor: | Yun Wang, Ying Zhang, Yong-Chao Li, Chang-Feng Li, Tian-Cheng Zhao, Dan-Dan Li |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
0301 basic medicine Cell Survival Receptors Retinoic Acid Down-Regulation Antineoplastic Agents Biology Biochemistry DNA Methyltransferase 3A 03 medical and health sciences Procaine 0302 clinical medicine Stomach Neoplasms Cell Line Tumor medicine Cyclin-Dependent Kinase Inhibitor p18 Humans Gene silencing DNA (Cytosine-5-)-Methyltransferases Enzyme Inhibitors Promoter Regions Genetic Molecular Biology Cyclin-Dependent Kinase Inhibitor p16 Cell Proliferation DNA Methylation Regulation Cancer Cell Biology DNA Methylation medicine.disease Molecular biology Gene Expression Regulation Neoplastic 030104 developmental biology CpG site 030220 oncology & carcinogenesis DNA methylation Cancer cell DNMT1 Cancer research CpG Islands medicine.drug |
| Zdroj: | Journal of Cellular Biochemistry. 119:2440-2449 |
| ISSN: | 1097-4644 0730-2312 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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