Role of arsenic (+3 oxidation state) methyltransferase in arsenic mediated APL treatment: an in vitro investigation

Metallomics : Integrated Biometal Science
Yasen MaimaitiyimingHua Naranmandura

Abstract

Arsenic (+3 oxidation state) methyltransferase (AS3MT) is a key enzyme responsible for arsenic metabolism in humans, which facilitates conversion of arsenic trioxide (As2O3) to more reactive metabolites such as monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII). However, it is unclear whether the biotransformation of arsenic by AS3MT contributes to the promotion of acute promyelocytic leukemia (APL) therapy. In order to understand the probable role of AS3MT in APL patients, we evaluated the effects of arsenite (iAsIII) and three mixed arsenicals (i.e., iAsIII, MMAIII and DMAIII, to mimic active arsenic species in the blood) on NB4 cell differentiation and apoptosis. Although the mixed arsenicals exhibited about 2 fold less effect on the induction of NB4 cell differentiation and PML-RARα fusion protein degradation, they showed 5 times stronger ability to induce apoptosis when compared with iAsIII. More importantly, the proliferation of NB4 cells was significantly (p < 0.05) inhibited in a transwell system co-cultured with AS3MT-transfected HepG2 cells after exposure to iAsIII, suggesting that the generation of methylated metabolites restrained cell proliferation. These findings indicate that the therapeutic effi...Continue Reading

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Citations

Jul 18, 2019·Metallomics : Integrated Biometal Science·Chang YangHua Naranmandura
Nov 9, 2018·Frontiers in Microbiology·Ibtissem Ben FekihCarlos Cervantes
Jan 14, 2020·Current Pharmacology Reports·Michael CoryellSeth T Walk
Nov 2, 2019·Metallomics : Integrated Biometal Science·Yasen MaimaitiyimingHua Naranmandura
Oct 31, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jing LuXin Hai

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Methods Mentioned

BETA
flow cytometry
transfection
PCR
electrophoresis

Software Mentioned

GraphPad Prism
GraphPad
Systat
Sigmaplot

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis