title: Phenylarsine Oxide Can Induce the Arsenite-Resistance Mutant PML Protein Solubility Changes.
abstract: Arsenic trioxide (As₂O₃) has recently become one of the most effective drugs for treatment of patient with acute promyelocytic leukemia (APL), and its molecular mechanism has also been largely investigated. However, it has been reported that As₂O₃ resistant patients are frequently found in relapsed APL after consolidation therapy, which is due to the point mutations in B-box type 2 motifs ofpromyelocytic leukemia(PML) gene. In the present study, we for the first time establish whether organic arsenic species phenylarsine oxide (PAO) could induce the mutant PML-IV (A216V) protein solubility changes and degradation. Here, three different PML protein variants (i.e., PML-IV, PML-V and mutant PML-A216V) were overexpressed in HEK293T cells and then exposed to PAO in time- and dose-dependent manners. Interestingly, PAO is found to have potential effect on induction of mutant PML-IV (A216V) protein solubility changes and degradation, but no appreciable effects were found following exposure to high concentrations of iAsIII, dimethylarsinous acid (DMAIII) and adriamycin (doxorubicin), even though they cause cell death. Our current data strongly indicate that PAO has good effects on the mutant PML protein solubility changes, and it may be helpful for improving the therapeutic strategies for arsenic-resistant APL treatments in the near future.
authors.affiliation: Department of Toxicology, School of Medicine and Public health, Zhejiang University, Hangzhou 310058, China. 21434054@zju.edu.cn.|Department of Marine Science, Ocean College, Zhejiang University, Hangzhou 310058, China. 21434054@zju.edu.cn.
authors.forename: Yu Han
authors.initials: YH
authors.lastname: Jiang
authors.affiliation: Department of Toxicology, School of Medicine and Public health, Zhejiang University, Hangzhou 310058, China. cyjdota@163.com.|Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China. cyjdota@163.com.
authors.forename: Ye Jia
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Toxicology, School of Medicine and Public health, Zhejiang University, Hangzhou 310058, China. 11618280@zju.edu.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Toxicology, School of Medicine and Public health, Zhejiang University, Hangzhou 310058, China. 21419019@zju.edu.cn.
authors.forename: Yong Fei
authors.initials: YF
authors.lastname: Lan
authors.affiliation: Department of Toxicology, School of Medicine and Public health, Zhejiang University, Hangzhou 310058, China. 11518283@zju.edu.cn.|Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China. 11518283@zju.edu.cn.
authors.forename: Chang
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Toxicology, School of Medicine and Public health, Zhejiang University, Hangzhou 310058, China. 11319039@zju.edu.cn.|College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. 11319039@zju.edu.cn.
authors.forename: Qian Qian
authors.initials: QQ
authors.lastname: Wang
authors.affiliation: Department of Toxicology, School of Medicine and Public health, Zhejiang University, Hangzhou 310058, China. liaqathussain@zju.edu.cn.|Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China. liaqathussain@zju.edu.cn.
authors.forename: Liaqat
authors.initials: L
authors.lastname: Hussain
authors.affiliation: Department of Toxicology, School of Medicine and Public health, Zhejiang University, Hangzhou 310058, China. yasinjan@zju.edu.cn.|Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China. yasinjan@zju.edu.cn.
authors.forename: Yasen
authors.initials: Y
authors.lastname: Maimaitiying
authors.affiliation: Department of Toxicology, School of Medicine and Public health, Zhejiang University, Hangzhou 310058, China. drkhairul16@gmail.com.
authors.forename: Khairul
authors.initials: K
authors.lastname: Islam
authors.affiliation: Department of Toxicology, School of Medicine and Public health, Zhejiang University, Hangzhou 310058, China. narenman@zju.edu.cn.|Department of Marine Science, Ocean College, Zhejiang University, Hangzhou 310058, China. narenman@zju.edu.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Naranmandura
mesh_terms: D001152:Arsenicals / Q000494:pharmacology*; D018053:Arsenites / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics*; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D000071156:Promyelocytic Leukemia Protein / Q000737:chemistry* / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D012995:Solubility / Q000187:drug effects
chemical_list: D001152:Arsenicals; D018053:Arsenites; D000071156:Promyelocytic Leukemia Protein; C029341:oxophenylarsine
keywords: acute promyelocytic leukemia; arsenic trioxide; arsenite; dimethylarsinous acid; monomethylarsonous acid; phenylarsine oxide; trivalent arsenicals