Resveratrol inhibits the tumor migration and invasion by upregulating TET1 and reducing TIMP2/3 methylation in prostate carcinoma cells

• Published in: The Prostate 2020-09, Vol.80 (12), p.977-985
• Main Authors: Wang, Kai, Chen, Zhen, Shi, Jian, Feng, Yuehua, Yu, Miaomei, Sun, Yangyang, Zhuang, Qianfeng, Liang, Bin, Luo, Guanghua, Xu, Xianlin, Fan, Min
• Format: Article
• Language: English
• Subjects: Cell adhesion & migration; Cell migration; Cytotoxicity; Demethylation; DNA methylation; Gelatinase A; Gelatinase B; Prostate; Prostate cancer; Prostate carcinoma; Resveratrol; Ribonucleic acid; RNA; ten‐eleven translocation 1; tissue inhibitor of metalloproteinase; Tissue inhibitor of metalloproteinase 2; Tissue inhibitor of metalloproteinase 3
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.24029

Background Recently, resveratrol (Res) has been suggested to suppress the migration and invasion of prostate cancer (PCa). In the present study, we aimed to investigate the effects of Res on genomic DNA methylation, as well as the migration and invasion of PCa cells. Methods The suppression by Res of the growth of PCa cells was verified through a cytotoxicity assay. In addition, the effects of Res on 5‐methylcytosine (5mC), 5‐hydroxymethylcytosine (5hmC), and ten‐eleven translocation 1 (TET1) levels were assessed, and the cell migration and invasion were also determined. The expressions of TET1, tissue inhibitor of metalloproteinases (TIMP) 2, TIMP3, MMP2, and MMP9 were detected through Western blot analysis. Afterward, TET1 was silenced using lentiviral short hairpin RNA to examine the effect of TET1 on the Res‐triggered inhibition of migration and invasion of PCa cells. Results Our results showed that Res upregulated the 5hmC and TET1 levels and downregulated the 5mC level. Moreover, Res also inhibited the migration and invasion of PCa cells, promoted the demethylation of TIMP2 and TIMP3 to upregulate their expressions, and suppressed the expressions of MMP2 and MMP9. The silencing of TET1 in the presence of Res showed that Res could exert its effect through TET1. Conclusions Our findings indicated that Res inhibited the migration and invasion of PCa cells via the TET1/TIMP2/TIMP3 pathway, which might potentially serve as a target for the treatment of PCa.