title: Arsenic trioxide induces apoptosis of p53 null osteosarcoma MG63 cells through the inhibition of catalase.
abstract: This study is aimed at investigating the effect of arsenic trioxide (ATO) on p53 null human osteosarcoma MG63 cells and the mechanisms underlying the effect. Apoptotic cells were detected by flow cytometry with Annexin-V-FITC/PI dual staining. Intracellular ROS was measured by flow cytometry using a cell-based ROS assay kit. Catalase activity and mRNAs were analyzed by ELISA and real-time qRT-PCR, respectively. Apoptosis and intracellular ROS of MG63 cells increased in a dose-dependent manner following arsenic treatments. Both were prevented by the presence of the anti-oxidative reagent N-acetyl-L: -cysteine (NAC) or catalase (CAT). Furthermore, the activity and mRNA of catalase were decreased strikingly following arsenic exposure. The present study indicates that p53 null osteosarcoma MG63 cells are susceptible to the ATO; the inhibition of catalase and the resulted intracellular ROS accumulation are an important molecular mechanism under which ATO induces apoptosis of p53-deficient osteosarcoma cells.
authors.affiliation: The Key Laboratory of Pathobiology, Ministry of Education, Jilin University, 130021 Changchun, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yudan
authors.initials: Y
authors.lastname: Wei
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Shi
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.forename: Ronggui
authors.initials: R
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002374:Catalase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002374:Catalase; D005978:Glutathione; D000077237:Arsenic Trioxide