Arsenite-induced apoptosis is prevented by selenite in A375 cell line.
Arsenic trioxide induces apoptosis and clinical remission in patients diagnosed with acute promyelocytic leukemia. The human malignant melanoma A375 cells were treated with NaAsO2 (0.1–130 μM) and also treated with combined 10 μM NaAsO2 and 10 μM Na2SeO3. NaAsO2 arrested cell growth in the G1 phase and induced apoptosis in a concentration- and time-dependent manner. In contrast, administration of Na2SeO3 antagonized the cell growth inhibition and apoptosis induced by NaAsO2. The NaAsO2 treatment resulted in a marked increase in p53 protein as early as 4 h and in Bcl-2 protein level by 12 h. In addition, p53 downregulation accompanied the combined treatment of NaAsO2 and Na2SeO3. Thus, our results indicate upregulation of p53 and Bcl-2 play acrucial role in the NaAsO2-induced G1 arrest and apoptosis of A375 cells and that downregulation p53 appears to contribute to the inhibition by Na2SeO3 of the effects induced by NaAsO2.
Wang
Zhi-Fang
ZF
Faculty of Public Health, College of Medicine, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi’an Jiaotong University, Xi’an, Shaanxi, China.
Guo
Xiong
X
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017670:Sodium Compounds / Q000494:pharmacology*; D018038:Sodium Selenite / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D018053:Arsenites; D019253:Proto-Oncogene Proteins c-bcl-2; D017670:Sodium Compounds; D016159:Tumor Suppressor Protein p53; C017947:sodium arsenite; D018038:Sodium Selenite