Genome-Wide Methylation Analysis Identifies NOX4 and KDM5A as Key Regulators in Inhibiting Breast Cancer Cell Proliferation by Ginsenoside Rg3

The American Journal of Chinese Medicine
Juyeon HamSun Jung Kim

Abstract

Ginsenoside Rg3 is a key metabolite of ginseng and is known to inhibit cancer cell growth. However, the epigenetics of CpG methylation and its regulatory mechanism have yet to be determined. Genome-wide methylation analysis of MCF-7 breast cancer cells treated with Rg3 was performed to identify epigenetically regulated genes and pathways. The effect of Rg3 on apoptosis and cell proliferation was examined by a colony formation assay and a dye-based cell proliferation assay. The association between methylation and gene expression was monitored by RT-PCR and Western blot analysis. Genome-wide methylation analysis identified the "cell morphology"-related pathway as the top network. Rg3 induced late stage apoptosis but inhibited cell proliferation up to 60%. Hypermethylated TRMT1L, PSMC6 and NOX4 were downregulated by Rg3, while hypomethylated ST3GAL4, RNLS and KDM5A were upregulated. In accordance, downregulation of NOX4 by siRNA abrogated the cell growth effect of Rg3, while the effect was opposite for KDM5A. Notably, breast cancer patients with a higher expression of NOX4 and KDM5A showed poor and good prognosis of survival, respectively. In conclusion, Rg3 deregulated tumor-related genes through alteration of the epigenetic meth...Continue Reading

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Citations

Jul 18, 2019·The American Journal of Chinese Medicine·Yalin ZhangJuan Kong
Aug 26, 2020·Archives of Pharmacal Research·Yujin JinKyung-Sun Heo
Dec 5, 2019·The American Journal of Chinese Medicine·Han XiaoJunling Yang
May 17, 2019·Indian Journal of Clinical Biochemistry : IJCB·Aman KumarRajendra Prasad
Feb 9, 2021·Free Radical Biology & Medicine·Alison C Brewer
Feb 19, 2021·Journal of Hematology & Oncology·Guan-Jun YangJiong Chen
Feb 25, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Heeok HongSeong Gu Hwang
Aug 23, 2021·Pathology, Research and Practice·Qianwei XingLimin Ma

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