title: Emodin targets mitochondrial cyclophilin D to induce apoptosis in HepG2 cells.
abstract: Emodin has demonstrated potent anticancer activity in human hepatocarcinoma cells and animal models, however, the cellular targets of emodin have not been fully defined. Here we report that emodin induces the dysfunction of mitochondria and the apoptosis in HepG2 cells through an enrichment in mitochondria. Specifically, A mitochondrial matrix protein (cyclophilin D, CyPD) is involved in emodin-induced apoptosis, and the inhibitor of CyPD (cyclosporin A) could almost completely suppressing the apoptosis; Moreover, as the expression of CyPD could be effectively inhibited by antioxidant N-acetyl-l-cysteine and epidermal growth factor (the activator of ERK), reactive oxygen species and ERK might be involved in the relevant role of CyPD. A further molecule-docking discloses the existence of three hydrogen-bonds in CyPD-emodin complex. Thus, target localization and CyPD in mitochondria provides an insight into the action of emodin in the treatment of liver cancer.
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Dian
authors.initials: D
authors.lastname: He
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Baitao
authors.initials: B
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address: zhenglf@lzu.edu.cn.
authors.forename: Lifang
authors.initials: L
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address: lijiazhong@lzu.edu.cn.
authors.forename: Jiazhong
authors.initials: J
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D004642:Emodin / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D017382:Reactive Oxygen Species; D016572:Cyclosporine; D021983:Cyclophilins; D004642:Emodin
keywords: Cyclophilin D; Emodin; Human hepatocarcinoma; Mitochondria; Molecule docking