Ginsenoside Rk1 induces cell cycle arrest and apoptosis in MDA-MB-231 triple negative breast cancer cells.
Toxicology. 2019 Feb 21. Epub 2019 Feb 21. PMID: 30797898
Ginsenoside Rk1 (Rk1) is a component presented in processed ginseng and it possess anti-insulin resistance, anti-inflammation and anti-cancer activities. However, there are few reports on the anti-triple negative breast cancer effect of Rk1. In this study, the anti-proliferation effects and mechanisms of Rk1 in MDA-MB-231 triple negative breast cancer cells were investigated. A breast cancer xenograft model showed that Rk1 significantly repressed tumor growth with low toxicity for major organs. Moreover, Rk1 dramatically inhibited cell proliferation, colony formation, promoted LDH release, and induced G/Gphase 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. Furthermore, Rk1 inhibited the phosphorylation of PI3K, Akt and mTOR. Pretreatment with pan-caspase inhibitor Z-VAD-FMK, PI3K specific inhibitor LY294002 and ROS scavenger N-acetylcysteine (NAC) further demonstrated that ROS/PI3K/Akt pathway was responsible for Rk1-induced apoptosis. Taken together, this work first illustrated the anti-triple negative breast cancer effects and mechanisms of Rk1 and ginsenoside Rk1 could be a new promising anti-tumor drug for breast cancer.