title: Oleanolic acid induces autophagic death in human gastric cancer cells in vitro and in vivo.
abstract: Oleanolic acid (OA), a plant-derived pentacyclic terpenoid, is known to have hepatoprotective effects. In this study, we found that OA induced autophagic cell death in multiple human gastric cancer cell lines. Moreover, OA-induced autophagy was shown for the first time in human gastric cancer cells, evidenced by the formation of GFP-RFP-LC3 puncta and autophagosomes. OA suppressed phospho-mTOR through inhibition of the PI3 K/AKT and ERK/p38 MAPK signalling pathways and through activation of the AMPK signalling pathway. Furthermore, we found that OA-induced cytotoxicity and autophagy could be blocked by the autophagy inhibitor 3-methyladenine or via siRNA targeting Beclin-1. Our in vivo research showed that OA delayed the formation of MGC-803 tumours in an autophagy-dependent manner. These results reveal a novel mechanism for OA in gastric cancer cells and suggest that OA could be a novel agent in the treatment of gastric cancer.
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zijingang Campus, Zhejiang University, Room 345, Hangzhou 310058, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Nie
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zijingang Campus, Zhejiang University, Room 345, Hangzhou 310058, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zijingang Campus, Zhejiang University, Room 345, Hangzhou 310058, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Institute of Biochemistry, College of Life Sciences, Zijingang Campus, Zhejiang University, Room 345, Hangzhou 310058, China.
authors.forename: Xing-Guo
authors.initials: XG
authors.lastname: Gong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1 / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009828:Oleanolic Acid / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D034741:RNA, Small Interfering; D009828:Oleanolic Acid; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: autophagic death; gastric cancer; in vivo; mTOR; oleanolic acid