title: An oxidative analogue of gambogic acid-induced apoptosis of human hepatocellular carcinoma cell line HepG2 is involved in its anticancer activity in vitro.
abstract: The objective of this study was to investigate the apoptosis-inducing effect of an oxidative analogue of gambogic acid (GA) on the human hepatocellular carcinoma cell line HepG2 and explore the related molecular mechanisms. HepG2 cells were treated with the analogue of GA and the growth inhibition was analysed by MTT assay. The morphological changes in cells were observed under an inverted light microscope and a fluorescence microscope. In addition, both the cell-cycle arrest and the apoptosis rate were detected by flow cytometry. Western blot was used to evaluate the alteration of protein expression. The viability of HepG2 cells was markedly inhibited in a concentration-dependent manner and obvious morphological changes were confirmed, including condensed chromatin and reduced volume. Increased percentage of apoptotic cells was displayed and altered expression level of several apoptosis-associated proteins, P53, Bcl-2, Bax and pro-caspase-3, was obtained. The newly synthesized analogue of GA exhibited potential anticancer activity, induced remarkable apoptosis in HepG2 cells, probably through the intrinsic mitochondrial pathway, and promised to be a new candidate for future cancer therapy.
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Tongjiaxiang, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Mu
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.forename: Yueheng
authors.initials: Y
authors.lastname: Yin
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Huan
authors.initials: H
authors.lastname: Gui
authors.forename: Qiong
authors.initials: Q
authors.lastname: Sun
authors.forename: Huaqin
authors.initials: H
authors.lastname: Duan
authors.forename: Lun
authors.initials: L
authors.lastname: Zhang
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Ke
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D010084:Oxidation-Reduction; D044004:Xanthones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D044004:Xanthones; C052659:gambogic acid