title: Olaquindox induces apoptosis through the mitochondrial pathway in HepG2 cells.
abstract: Olaquindox is used in China as feed additive for growth promotion in pigs. Recently, we have demonstrated that olaquindox induced genome DNA damage and oxidative stress in HepG2 cells. The aim of this study was to explore the molecular mechanism of cell cycle arrest and apoptosis induced by olaquindox in HepG2 cells. In the present study olaquindox induced cell cycle arrest to the S phase and dose-dependent apoptotic cell death in HepG2 cells, indicated by accumulation of sub-G1 cell population, nuclear condenstion, DNA fragmentation, caspases activation and PARP cleavage. Meanwhile, the data showed that olaquindox triggered ROS-mediated apoptosis in HepG2 cells correlated with both the mitochondrial DNA damage and nuclear DNA damage, collapse of Δψ(m), opening of mPTP, down-regulation of Bcl-2 and up-regulation of Bax. Furthermore, we also found that olaquindox increased the expression of p53 protein and induced the release of cytochrome C from mitochondria to cytosol. In conclusion, olaquindox induced apoptosis of HepG2 cells through a caspase-9 and -3 dependent mitochondrial pathway, involving p53, Bcl-2 family protein expression, Δψ(m) disruption and mPTP opening.
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, PR China.
authors.forename: Jiajie
authors.initials: J
authors.lastname: Zou
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Jin
authors.forename: Shusheng
authors.initials: S
authors.lastname: Tang
authors.forename: Kaipao
authors.initials: K
authors.lastname: Chen
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Xilong
authors.initials: X
authors.lastname: Xiao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011810:Quinoxalines / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D011810:Quinoxalines; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; C013168:olaquindox