title: Dihydroartemisinin-induced inhibition of proliferation in BEL-7402 cells: an analysis of the mitochondrial proteome.
abstract: Artemisinin, the active ingredient of the Chinese medicinal herb Artemisia annua L., and its derivatives (ARTs) are currently widely used as anti-malarial drugs around the world. In this study, we found that dihydroartemisinin (DHA), one of the main active metabolites of ARTs, inhibited the proliferation of human hepatocarcinoma BEL-7402 cells in a concentration-dependent manner. To interpret the mechanisms involved, an analysis of the mitochondrial proteome was performed employing two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Seven mitochondrial proteins including fumarate hydratase, 60 kDa heat shock protein, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, two subunits of ATP synthase and NADPH:adrenodoxin oxidoreductase were identified to be differentially expressed between the control and DHA-treated groups. Our results indicate that the imbalance of energy metabolism induced by DHA may contribute, at least in part, to its anti-cancer potential in BEL-7402 cells.
authors.affiliation: College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, PR China. jinjian.lu@163.com
authors.forename: Jin-Jian
authors.initials: JJ
authors.lastname: Lu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: De-Zhao
authors.initials: DZ
authors.lastname: Lu
authors.forename: Xing-De
authors.initials: XD
authors.lastname: Wo
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Shi
authors.forename: Tao-Qi
authors.initials: TQ
authors.lastname: Lin
authors.forename: Mi-Mi
authors.initials: MM
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Tang
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000032:analysis; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D031172:Artemisia annua / Q000737:chemistry; D037621:Artemisinins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D015180:Electrophoresis, Gel, Two-Dimensional; D004734:Energy Metabolism; D004746:Enoyl-CoA Hydratase / Q000032:analysis; D005649:Fumarate Hydratase / Q000032:analysis; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D024101:Mitochondrial Proteins / Q000032:analysis*; D025261:Mitochondrial Proton-Translocating ATPases / Q000032:analysis; D020543:Proteome / Q000032:analysis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D037621:Artemisinins; D024101:Mitochondrial Proteins; D020543:Proteome; C039060:artenimol; D015094:3-Hydroxyacyl CoA Dehydrogenases; D025261:Mitochondrial Proton-Translocating ATPases; D004746:Enoyl-CoA Hydratase; D005649:Fumarate Hydratase