Ginsenoside Rh2 inhibits breast cancer cell growth via ERβ-TNFα pathway

Acta Biochim Biophys Sin (Shanghai). 2022 May 25;54(5):647-656. doi: 10.3724/abbs.2022039.

Abstract

Ginsenoside Rh2 is one of rare panaxidiols extracted from Panax ginseng and a potential estrogen receptor ligand that exhibits moderate estrogenic activity. However, the effect of Rh2 on growth inhibition and its underlying molecular mechanism in human breast cells are not fully understood. In this study, we tested cell viability by MTT and colony formation assays. Cell growth and cell cycle were determined to investigate the effect of ginsenoside Rh2 by flow cytometry. The expressions of estrogen receptors (ERs), TNFα, and apoptosis-related proteins were detected by qPCR and western blot analysis. The mechanisms of ERα and ERβ action were determined using transfection and inhibitors. Antitumor effect of ginsenoside Rh2 against MCF-7 cells was investigated in xenograft mice. Our results showed that ginsenoside Rh2 induced apoptosis and G1/S phase arrest in MCF-7 cells. Treatment of cells with ginsenoside Rh2 down-regulated protein levels of ERα, and up-regulated mRNA and protein levels of ERβ and TNFα. We also found that ginsenoside Rh2-induced TNFα over-expression is through up-regulation of ERβ initiated by ginsenoside Rh2. Furthermore, ginsenoside Rh2 induced MCF-7 cell apoptosis via estrogen receptor β-TNFα pathway in vivo. These results demonstrate that ginsenoside Rh2 promotes TNFα-induced apoptosis and G1/S phase arrest via regulation of ERβ.

Keywords: TNFα; apoptosis; breast cancer; estrogen receptor; ginsenoside Rh2.

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Cell Proliferation
  • Estrogen Receptor alpha
  • Estrogen Receptor beta / genetics
  • Female
  • Ginsenosides* / pharmacology
  • Humans
  • Ligands
  • Mice
  • RNA, Messenger
  • Receptors, Estrogen
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Apoptosis Regulatory Proteins
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • ginsenoside Rh2
  • Ginsenosides
  • Ligands
  • Receptors, Estrogen
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha

Grants and funding

This work was supported by the grants from the National Natural Science Foundation of China (Nos. 81973710, 81903107, 81874332 and 81673544), the Hunan Provincial Natural Science Foundation of China (Nos. 2021JJ30902 and 2020JJ8052), the Health Commission Key Program of Hunan Province (No. 202102021395), the Hunan Provincial Key Program for Research and Development (No. 2018SK21310), and the Graduate research innovation project of Central South University (Nos. 2018zzts118 and 1053320192015).