title: Up-regulation of antioxidant enzymes and coenzyme Q(10) in a human oral cancer cell line with acquired bleomycin resistance.
abstract: Bleomycin (BLM) is an anti-cancer drug that can induce formation of reactive oxygen species (ROS). To investigate the association between up-regulation of antioxidant enzymes and coenzyme Q(10) (CoQ(10)) in acquired BLM resistance, one BLM-resistant clone, SBLM24 clone, was selected from a human oral cancer cell line, SCC61 clone. The BLM resistance of SBLM24 clone relative to a sub-clone of SCC61b cells was confirmed by analysis of clonogenic ability and cell cycle arrest. CoQ(10) levels and levels of Mn superoxide dismutase, glutathione peroxidase 1, catalase and thioredoxin reductase 1 were augmented in SBLM24 clone although there was also a mild increase in the expression of BLM hydrolase. Suppression of CoQ(10) levels by 4-aminobenzoate sensitized BLM-induced cytotoxicity. The results of suppression on enhanced ROS production by BLM and the cross-resistance to hydrogen peroxide in SBLM24 clone further demonstrated the development of adaptation to oxidative stress during the formation of acquired BLM resistance.
authors.affiliation: Department and Graduate Institute of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan, Republic of China. yen@mail.cgu.edu.tw
authors.forename: Hsiu-Chuan
authors.initials: HC
authors.lastname: Yen
authors.forename: Sin-Hua
authors.initials: SH
authors.lastname: Li
authors.forename: Hideyuki J
authors.initials: HJ
authors.lastname: Majima
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Huang
authors.forename: Chiu-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Liu
authors.forename: Ya-Chi
authors.initials: YC
authors.lastname: Tu
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Chen
mesh_terms: D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell; D002374:Catalase / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D057075:Enzyme Assays; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009062:Mouth Neoplasms; D016877:Oxidants / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism; D015854:Up-Regulation; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D016877:Oxidants; D017382:Reactive Oxygen Species; D001761:Bleomycin; D014803:Vitamin B Complex; D014451:Ubiquinone; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase; C024989:coenzyme Q10; D010129:4-Aminobenzoic Acid