1. Academic Validation
  2. Ginsenoside Rk1 induces cell cycle arrest and apoptosis in MDA-MB-231 triple negative breast cancer cells

Ginsenoside Rk1 induces cell cycle arrest and apoptosis in MDA-MB-231 triple negative breast cancer cells

  • Toxicology. 2019 Apr 15;418:22-31. doi: 10.1016/j.tox.2019.02.010.
Yinan Hong 1 Daidi Fan 2
Affiliations

Affiliations

  • 1 Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 Taibai North Road, Xi'an, Shaanxi, 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, 229 Taibai North Road, Xi'an, Shaanxi, 710069, China; Biotech. & Biomed. Research Institute, Northwest University, 229 Taibai North Road, Xi'an, Shaanxi 710069, China.
  • 2 Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, 229 Taibai North Road, Xi'an, Shaanxi, 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, 229 Taibai North Road, Xi'an, Shaanxi, 710069, China; Biotech. & Biomed. Research Institute, Northwest University, 229 Taibai North Road, Xi'an, Shaanxi 710069, China. Electronic address: fandaidi@nwu.edu.cn.
Abstract

Ginsenoside Rk1 (Rk1) is a component found in processed ginseng that exhibits anti-insulin resistance, anti-inflammation and anti-cancer activities. However, there are few reports of Rk1 activity against triple negative breast Cancer (TNBC). In this study, the anti-proliferation and potential mechanisms of Rk1 in MDA-MB-231 cells were investigated. Xenograft model exhibited that Rk1 significantly repressed tumor growth with low toxicity to major organs. Moreover, Rk1 dramatically inhibited cell proliferation, colony formation, promoted LDH release, and induced G0/G1 phase arrest. Rk1 also triggered intracellular Reactive Oxygen Species (ROS) generation and mitochondrial membrane potential reduction. Western blot results revealed that Rk1 increased the expression of Bax, cytochrome C, cleaved Caspase 3, 8 and 9 levels and decreased Bcl-2 level and blocked the PI3K/Akt pathway. Pretreatment with the pan-caspase inhibitor Z-VAD-FMK, PI3K/Akt pathway activator Insulin or ROS scavenger N-acetylcysteine (NAC) further demonstrated that ROS/PI3K/Akt pathway was responsible for Rk1-induced Apoptosis. Overall, this is the first study to illustrate the anti-triple negative breast Cancer effects and mechanisms of Rk1 and ginsenoside Rk1 could be a new promising anti-tumor drug for TNBC.

Keywords

Apoptosis; Cell cycle arrest; Ginsenoside Rk1; MDA-MB-231 cells; ROS/PI3K/Akt signaling pathway.

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