Effects of ginsenoside Rg3 on epigenetic modification in ovarian cancer cells

Abstract

Epigenetic modifications are closely related to oncogene activation and tumor suppressor gene inactivation. The aim of this study was to determine the effects of ginsenoside Rg3 on epigenetic modification in ovarian cancer cells. Cell proliferation, metastasis, invasion and apoptosis were respectively determined using Cell Counting Kit-8 (CCK-8), wound healing, Transwell and flow cytometric assays. Methylation levels were determined using methylation specific PCR (MSP). Related-factor expression was detected by conducting real-time-qPCR (RT-qPCR) and western blotting. The results revealed that cell proliferation was inhibited by ginsenoside Rg3 (0, 25, 50, 100 and 200 µg/ml) in a time-dependent manner (12, 24 and 48 h). Ginsenoside Rg3 (50, 100 and 200 µg/ml) was selected to treat cells in various experiments. When ovarian cells were treated with ginsenoside Rg3, cell apoptosis was observed to be promoted, while cell metastasis and invasion were inhibited at 48 h. The results of the present study revealed that in the promoter regions of p53, p16 and hMLH1, the methylation levels decreased, while the mRNA and protein levels significantly increased. The activities of DNMTs and mRNA as well as protein levels of DNMT1, DNMT3a and DNMT3b were decreased by Rg3. The data also demonstrated that the mRNA and protein levels of acetyl-H3 K14/K9 and acetyl-H4 K12/K5/K16 were increased by Rg3. Hence, ginsenoside Rg3 inhibited ovarian cancer cell viability, migration and invasion as well as promoted cell apoptosis.

DNA Methyltransferases in Cancer: Biology, Paradox, Aberrations, and Targeted Therapy

“…Zhao et al found that the increased expression of DNMT3B in ovarian cancer cells increased the methylation level of the promoter regions of anti-oncogenes such as hMLH1 (mismatch repair gene human mutL homolog-1), p16 and p53 . These methylation changes decreased the expression of the hMLH1 , p16 and p53 genes and promoted tumor development [ 42 , 107 ]. As mentioned above, decitabine is a specific DNMT inhibitor, which can partially reverse DNA methylation.…”

Identification of LncRNA Prognostic Markers for Ovarian Cancer by Integration of Co-expression and CeRNA Network

“…There is an urgent need for effective prognostic markers to improve OC overall survival ( Powell et al, 2005 ; Shen et al, 2017 ; Tong et al, 2019 ; Zhao et al, 2019 ). Immune cells can enhance anticancer immune responses by recognizing cancer antigens, indicating that they may influence cancer prognosis ( Drakes and Stiff, 2018 ).…”

Ginsenoside Rg3 suppresses ovarian cancer cell proliferation and invasion by inhibiting the expression of lncRNA H19

“…In recent years, related studies suggested the antiovarian cancer effect of ginsenoside Rg3 (Zheng et al, 2017;Zheng et al, 2018;Liu et al, 2017;. Interestingly, our previous results revealed that ginsenoside Rg3 inhibited cell proliferation, migration and invasion but promoted apoptosis in SKOV3 ovarian cancer cells (Zhao et al, 2019). Moreover, ginsenoside Rg3 decreased hypermethylation of CpG islands in the promoter region of tumor suppressor genes (p53, p16 and hMLH1), reduced the expression levels of DNA cytosine methyltransferases (DNMT1, DNMT3a and DNMT3b), and inhibited the activities of histone deacetylases (HDACs) (Zhao et al, 2019).…”

“…Interestingly, our previous results revealed that ginsenoside Rg3 inhibited cell proliferation, migration and invasion but promoted apoptosis in SKOV3 ovarian cancer cells (Zhao et al, 2019). Moreover, ginsenoside Rg3 decreased hypermethylation of CpG islands in the promoter region of tumor suppressor genes (p53, p16 and hMLH1), reduced the expression levels of DNA cytosine methyltransferases (DNMT1, DNMT3a and DNMT3b), and inhibited the activities of histone deacetylases (HDACs) (Zhao et al, 2019). All of these findings suggested that ginsenoside Rg3 may have potential anticancer activity in OC.…”