title: Camptothecin-20(s)-O-[N-(3'α,12'α-dihydroxy-24'-carbonyl-5'β-cholan)]-lysine, a novel camptothecin analogue, induces apoptosis towards hepatocellular carcinoma SMMC-7721 cells.
abstract: Camptothecin-20(s)-O-[N-(3'α,12'α-dihydroxy-24'-carbonyl-5'β-cholan)]-lysine (B2) is a novel camptothecin analogue. Our previous study had shown that it displayed higher cytoxicity activity towards hepatocellular carcinoma SMMC-7721 cells than camptothecin (CPT) in vitro. In this paper, the underlying mechanism of anti-proliferation of B2 towards SMMC-7721 cells was further examined. Cell growth inhibition of B2 was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; morphological changes were observed under Laser Scanning Confocal Microscope (LSCM); cell cycle distribution, apoptotic population, changes in mitochondrial membrane potential, intracellular calcium concentration and reactive oxygen species (ROS) production were determined by flow cytometry (FCM). Activities of caspase-3 and caspase-9 were measured, and the expression level of Bcl-2 and Bax proteins were analyzed by Western blot. The results suggested that B2 inhibited SMMC-7721 cell growth by causing cell cycle arrest at the S and G2/M phases, and induced apoptosis involving a mitochondrial pathway. B2 appears to cause a high induction of apoptosis on SMMC-7721 cells in vitro, which suggests it might be a potential drug for cancer therapy.
authors.affiliation: The Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin 150040, China. li_qingyong@126.com
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Qiu
authors.forename: Qiaochu
authors.initials: Q
authors.lastname: Zhu
authors.forename: Yuangang
authors.initials: Y
authors.lastname: Zu
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Deng
authors.forename: Tengfei
authors.initials: T
authors.lastname: Zhao
authors.forename: Chunfei
authors.initials: C
authors.lastname: Jiang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C572585:camptothecin-20(s)-O-(N-(3'alpha,12alpha-dihydroxy-24'-carbonyl-5'beta-cholan))-lysine; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D002118:Calcium; D002166:Camptothecin