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Int. J. Mol. Sci. 2017, 18(2), 247; doi:10.3390/ijms18020247

Phenylarsine Oxide Can Induce the Arsenite-Resistance Mutant PML Protein Solubility Changes

1
Department of Toxicology, School of Medicine and Public health, Zhejiang University, Hangzhou 310058, China
2
Department of Marine Science, Ocean College, Zhejiang University, Hangzhou 310058, China
3
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China
4
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editors: Yasumitsu Ogra and Takafumi Hirata
Received: 4 January 2017 / Revised: 17 January 2017 / Accepted: 18 January 2017 / Published: 25 January 2017
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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 of promyelocytic 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. View Full-Text
Keywords: arsenite; acute promyelocytic leukemia; arsenic trioxide; monomethylarsonous acid; dimethylarsinous acid; phenylarsine oxide; trivalent arsenicals arsenite; acute promyelocytic leukemia; arsenic trioxide; monomethylarsonous acid; dimethylarsinous acid; phenylarsine oxide; trivalent arsenicals
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MDPI and ACS Style

Jiang, Y.H.; Chen, Y.J.; Wang, C.; Lan, Y.F.; Yang, C.; Wang, Q.Q.; Hussain, L.; Maimaitiying, Y.; Islam, K.; Naranmandura, H. Phenylarsine Oxide Can Induce the Arsenite-Resistance Mutant PML Protein Solubility Changes. Int. J. Mol. Sci. 2017, 18, 247.

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