20(S)-ginsenoside Rh2 displays efficacy against T-cell acute lymphoblastic leukemia through PI3K/Akt/mTOR signal pathway

Abstract Backgroud T-cell acute lymphoblastic leukemia (T-ALL) is a kind of aggressive hematological cancer, and PI3K/Akt/mTOR signaling pathway is activated in most T-ALL patients and responsible for poor prognosis. 20(S)-ginsenoside Rh2 (20(S)-GRh2) is a major active compound extracted from ginseng, which exhibits anti-cancer effects. However, the underlying anti-cancer mechanisms of 20(S)-GRh2 targeting PI3K/Akt/mTOR pathway in T-ALL have not been explored. Methods Cells growth and cell cycle were determined to investigate the effect of 20(S)-GRh2 on ALL cells. PI3K/Akt/mTOR pathway-related proteins were detected in 20(S)-GRh2-treated Jurkat cells by immunoblotting. Antitumor effect of 20(S)-GRh2 against T-ALL was investigated in xenograft mice. The mechanisms of 20(S)-GRh2 against T-ALL were examined by cell proliferation, apoptosis and autophagy. Results In the present study, the results showed that 20(S)-GRh2 decreased cell growth and arrested cell cycle at G1 phase in ALL cells. 20(S)-GRh2 induced apoptosis through enhancing reactive oxygen species (ROS) generation and up-regulating apoptosis-related proteins. 20(S)-GRh2 significantly elevated the levels of pEGFP-LC3 and autophagy-related proteins in Jurkat cells. Furthermore, PI3K/Akt/mTOR signaling pathway was effectively blocked by 20(S)-GRh2. 20(S)-GRh2 suppressed cell proliferation and promoted apoptosis and autophagy by suppressing PI3K/Akt/mTOR pathway in Jurkat cells. Finally, 20(S)-GRh2 alleviated symptoms of leukemia and reduced the number of white blood cells and CD3 staining in spleen of xenograft mice, indicating antitumor effects against T-ALL in vivo. Conclusion The findings indicate that 20(S)-GRh2 exhibits beneficial effects against T-ALL through PI3K/Akt/mTOR pathway and could be a natural product of novel target for T-ALL therapy.