title: AKT/mTOR signaling pathway is involved in salvianolic acid B-induced autophagy and apoptosis in hepatocellular carcinoma cells.
abstract: 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.
authors: Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors: Ling
authors: L
authors: Gong
authors: Department of Laboratory, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors: Chunhong
authors: C
authors: Di
authors: Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors: Xiaofang
authors: X
authors: Xia
authors: Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors: Jie
authors: J
authors: Wang
authors: Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors: Gongying
authors: G
authors: Chen
authors: Department of Liver Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
authors: Junping
authors: J
authors: Shi
authors: Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors: Pengshuai
authors: P
authors: Chen
authors: Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors: Hui
authors: H
authors: Xu
authors: Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors: Weibing
authors: W
authors: Zhang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1 / Q000235:genetics; D001572:Benzofurans / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002738:Chloroquine / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D027561:Salvia miltiorrhiza; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D053630:Depsides
chemical_list: D000225:Adenine; D000970:Antineoplastic Agents; D000071186:Beclin-1; D001572:Benzofurans; D002738:Chloroquine; D004365:Drugs, Chinese Herbal; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases; C028972:dan-shen root extract; C025946:3-methyladenine; C076944:salvianolic acid B; D053630:Depsides; C546842:MTOR protein, human