Effects of R type and S type ginsenoside Rg3 on DNA methylation in human hepatocarcinoma cells

Abstract

Ginsenoside Rg3, a bioactive constituent isolated from Panax ginseng, exhibits antitumorigenic, antioxidative, antiangiogenic, neuroprotective and other biological activities are associated with the regulation of multiple genes. DNA methylation patterns, particularly those in the promoter region, affect gene expression, and DNA methylation is catalyzed by DNA methylases. However, whether ginsenoside Rg3 affects DNA methylation is unknown. High performance liquid chromatography assay, MspI/HpaII polymerase chain reaction (PCR) and reverse transcription-quantitative PCR were performed to assess DNA methylation. It was demonstrated that 20(S)-ginsenoside Rg3 treatment resulted in increased inhibition of cell growth, compared with treatment with 20(R)-ginsenoside Rg3 in the human HepG2 hepatocarcinoma cell line. It was additionally revealed that treatment with 20(S)-ginsenoside Rg3 reduced global genomic DNA methylation, altered cystosine methylation of the promoter regions of P53, B cell lymphoma 2 and vascular endothelial growth factor, and downregulated the expression of DNA methyltransferase (DNMT) 3a and DNMT3b more than treatment with 20(R)-ginsenoside Rg3 in HepG2 cells. These results revealed that the modulation of DNA methylation may be important in the pharmaceutical activities of ginsenoside Rg3.

Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer

“…The 20(S)-Rg3 was also a better scavenger of hydroxyl radicals [23] and in the human gastric cancer cell line AGS, was responsible for inducing apoptosis (through activation of caspase-3, -8, and -9) [24]. In human hepatocellular carcinoma cell line HepG2, 20(S)-Rg3 was the more effective epimer in inhibiting cell growth, downregulating the expression of DNA methyltransferases, reducing global DNA methylation, and in particular, modifying the methylation of the promoter region of some relevant genes in cancer such as VEGF, TP53, and BCL-2 [25].…”

“…Regardless of the stereotype, Rg3 has been studied in several cancer models and various mechanisms are suggested for its actions. These mechanisms include induction of apoptosis [24,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52], induction of autophagy through upregulation of autophagy-associated molecules [53], inhibition of proliferation [24,25,38,41,42,44,45,46,50,51,54,55,56,57,58,59,60,61,62,63], inhibition of metastasis [29,50,62,64,65,66,67,68,69,70,71] and angiogenesis [55,56,66], cell cycle arrest [47], immunomodulatory effects [72], sensitization to radiation [73], reducing multid...…”

Ginsenoside Rg3 Prevents Oncogenic Long Noncoding RNA ATXN8OS from Inhibiting Tumor-Suppressive microRNA-424-5p in Breast Cancer Cells

“…Notably, NOX4 and KDM5A were hyper- and hypo-methylated on their promoter regions, respectively, which led to gene dysregulation and increases in cell apoptosis [ 8 ]. Other genes such as p53, Bcl-2, and EGF were affected by Rg3-mediated promoter methylation in the HepG2-hepatocarcinoma cell line [ 9 ]. Approximately a dozen (microRNAs) miRs are known to be regulated by Rg3, many of which are involved in cancer malignancy, metastasis, or EMT [ 10 , 11 ].…”

Ginsenoside Rg3 and Korean Red Ginseng extract epigenetically regulate the tumor-related long noncoding RNAs RFX3-AS1 and STXBP5-AS1

“…For example, P53 is a well-known tumor suppressor that is promoted by Rg3 treatment in gallbladder cancer cells [7], while the oncogenes C/EBPβ [3], HIF1α [8], and MMP-9 [9] are downregulated by Rg3 in a variety of cancer cells. Recently, Rg3 was shown to epigenetically regulate tumor-related genes by modulating the methylation of cytosine residue at the promoter [10]. In addition, BCL2 and VEGF proto-oncogenes are hypermethylated and P53 is hypomethylated by Rg3 in HepG2 hepatocarcinoma cells.…”