salvianolic-acid-B and Carcinoma--Hepatocellular

Chinese medicines are emerging as an attractive new generation of anticancer drugs. Here, we explored the impact of salvianolic acid B (Sal B), the major water-soluble compounds of Danshen, on apoptosis and autophagy of human hepatocellular carcinoma cells (HCC). We also investigated the related molecular mechanisms. We found that Sal B exhibits potent ability to inhibit HCC cells viability in a concentration-dependent manner, and to induce apoptosis via the mitochondrial apoptosis pathway. Additionally, Sal B could also induce autophagy. Furthermore, pretreatment with the autophagy inhibitor chloroquine or 3-methyladenine showed the potential in attenuating the apoptosis rate induced by Sal B. Mechanistically, Sal B treatment inhibited the AKT/mTOR signaling cascade in vitro. Overexpression of AKT abolished the effects of Sal B on HCC cells, suggesting a critical role of the AKT/mTOR signaling pathway in Sal B-induced biological effects. Our results indicated that the mitochondrial pathway was involved in Sal B-induced apoptosis of HCC cells. Moreover, the AKT/mTOR signaling pathway was involved in Sal B-induced autophagy, which promoted apoptosis. This study may provide a promising strategy for using Sal B as a chemotherapeutic agent for patients with HCC.

Topics: Adenine; Antineoplastic Agents; Apoptosis; Autophagy; Beclin-1; Benzofurans; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Chloroquine; Drugs, Chinese Herbal; Humans; Liver Neoplasms; Mitochondria; Proto-Oncogene Proteins c-akt; RNA Interference; RNA, Small Interfering; Salvia miltiorrhiza; Signal Transduction; TOR Serine-Threonine Kinases