title: Oleanolic acid induces mitochondrial-dependent apoptosis and G0/G1 phase arrest in gallbladder cancer cells.
abstract: Oleanolic acid (OA), a naturally occurring triterpenoid, exhibits potential antitumor activity in many tumor cell lines. Gallbladder carcinoma is the most common malignancy of the biliary tract, and is a highly aggressive tumor with an extremely poor prognosis. Unfortunately, the effects of OA on gallbladder carcinoma are unknown. In this study, we investigated the effects of OA on gallbladder cancer cells and the underlying mechanism. The results showed that OA inhibits proliferation of gallbladder cancer cells in a dose-dependent and time-dependent manner on MTT and colony formation assay. A flow cytometry assay revealed apoptosis and G0/G1 phase arrest in GBC-SD and NOZ cells. Western blot analysis and a mitochondrial membrane potential assay demonstrated that OA functions through the mitochondrial apoptosis pathway. Moreover, this drug inhibited tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data suggest that OA inhibits proliferation of gallbladder cancer cells by regulating apoptosis and the cell cycle process. Thus, OA may be a promising drug for adjuvant chemotherapy in gallbladder carcinoma.
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Huai-Feng
authors.initials: HF
authors.lastname: Li
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xu-An
authors.initials: XA
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Xiang
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Hu
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Shu
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Mao-Lan
authors.initials: ML
authors.lastname: Li
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xiang-Song
authors.initials: XS
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Ye
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Weng
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Run-Fa
authors.initials: RF
authors.lastname: Bao
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Laboratory of General Surgery, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China ; Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: Ying-Bin
authors.initials: YB
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase / Q000187:drug effects*; D005706:Gallbladder Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects*; D009828:Oleanolic Acid / Q000494:pharmacology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D009828:Oleanolic Acid; C022616:thiazolyl blue
keywords: apoptosis; cell cycle arrest; gallbladder carcinoma; mitochondrial pathway; oleanolic acid