Ginsenoside Rk1 induces cell death through ROS-mediated PTEN/PI3K/Akt/mTOR signaling pathway in MCF-7 cells

[Display omitted] •Rk1 triggered S phase arrest in MCF-7 cells.•Rk1 induced extrinsic and intrinsic apoptotic pathway.•ROS-mediated PTEN/PI3K/Akt/mTOR pathway was involved in Rk1-induced cell death.•Rk1 suppressed tumor growth with low toxicity for major organs in vivo. Ginsenosides have been reported to possess pharmacological effects, such as antioxidative, anti-inflammatory and antitumor effects. Nevertheless, little has been reported about the anti-breast cancer effects of ginsenoside Rk1 (Rk1). In this work, we explored the anti-breast cancer effects of Rk1. The results suggested that Rk1 suppressed cell growth, colony formation, and triggered S phase arrest. Rk1 also triggered ROS overproduction, reduced mitochondrial membrane potential and induced apoptosis. Moreover, the PTEN/PI3K/Akt/mTOR pathway was involved in Rk1-induced apoptosis. Treatment with Z-VAD-FMK, LY294002 and N-acetylcysteine further illustrated that Rk1 induced apoptosis in MCF-7 cells through ROS-mediated PTEN/PI3K/Akt/mTOR signaling pathway. Furthermore, in xenograft nude mice model, Rk1 treatment dramatically suppressed tumor growth and caused no obvious injuries to major organs. Taken together, the results of this study demonstrated, for the first time, the anticancer efficacy and mechanism of Rk1 in MCF-7 cells, providing basic evidence supporting Rk1 as a potential anti-breast cancer agent.