title: Salvianolic acid B, a novel autophagy inducer, exerts antitumor activity as a single agent in colorectal cancer cells.
abstract: Salvianolic Acid B (Sal B), an active compound extracted from the Chinese herb Salvia miltiorrhiza, is attracting more and more attention due to its biological activities, including antioxidant, anticoagulant and antitumor effects. However, autophagy induction in cancer cells by Sal B has never been recognized. In this study, we demonstrated that Sal B induced cell death and triggered autophagy in HCT116 and HT29 cells in a dose-dependent manner. Specific inhibition of autophagy by 3-MA or shRNA targeting Atg5 rescued Sal B-induced cell death in vitro and in vivo, suggesting that Sal B-induced autophagy may play a pro-death role and contribute to the cell death of colorectal cancer cell lines. Furthermore, AKT/mTOR signaling pathway was demonstrated to be a critical mediator in regulating Sal B-induced cell death. Overexpression of AKT by the transfection with AKT plasmid or pretreatment with insulin decreased Sal B-induced autophagy and cell death. Inversely, inhibition of AKT by LY294002 treatment markedly enhanced Sal B-induced autophagy and cell death. Taken together, our results demonstrate, for the first time, that Sal B is a novel autophagy inducer and exerts its antitumor activity as a single agent in colorectal cancer cells through the suppression of AKT/mTOR pathway.
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.|Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Jing
authors.affiliation: Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Fei
authors.affiliation: Department of Surgical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Jichun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Lumin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Liuxi
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.affiliation: Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.|Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.|Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Xinbing
authors.initials: X
authors.lastname: Sui
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.|Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.|Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Pan
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000071182:Autophagosomes / Q000187:drug effects / Q000648:ultrastructure; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5 / Q000235:genetics / Q000378:metabolism; D001572:Benzofurans / Q000494:pharmacology / Q000627:therapeutic use*; D002867:Chromones / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009025:Morpholines / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D053630:Depsides
chemical_list: D000225:Adenine; D000970:Antineoplastic Agents; D000071187:Autophagy-Related Protein 5; D001572:Benzofurans; D002867:Chromones; D004365:Drugs, Chinese Herbal; D009025:Morpholines; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases; C502778:ATG5 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C025946:3-methyladenine; C076944:salvianolic acid B; D053630:Depsides; C546842:MTOR protein, human
keywords: autophagy; cell death; colorectal cancer; natural compound; salvianolic acid B