Total saponins isolated from Radix et Rhizoma Leonticis suppresses tumor cells growth by regulation of PI3K/Akt/mTOR and p38 MAPK pathways

Abstract

Both PI3K/AKT/mTOR and mitogen activated protein kinase (MAPK) signaling cascades played an important role in tumorigenesis, a more complete understanding of these signaling pathways allowed the development of new therapeutic strategies. Total saponins isolated from Radix et Rhizoma Leonticis (RLTS) was recognized with anticancer properties. In a murine hepatocellular carcinoma H22 cell-bearing mouse model, RLTS exhibited significant inhibitory effect on tumor growth. Here, we investigated the role of RLTS on the PI3K/AKT/mTOR signaling pathway and MAPK pathways in liver and lung cancer cells. Results obtained showed RLTS inhibited cell proliferation and induced cell apoptosis in vitro, which attributed to the inhibition on the activation of PI3K/AKT/mTOR cascade and its related signaling molecules, such as activated VEGFR and NF-κB, and activation of p38 MAPK in tumor cells. Additional, RLTS inhibited cell migration and downregulated proteins that mediated metastasis including CXCR4, MMP2 and MMP9. Overall, these findings suggested that RLTS interfered with multiple signaling cascades involved in tumorigenesis and had potential in cancer therapy.

Keywords: Hepatocellular carcinoma; Lung cancer; PI3K/Akt/mTOR; Total saponins; p38 MAPK.