Biocompatible arsenic trioxide nanoparticles induce cell cycle arrest by p21(WAF1/CIP1) expression via epigenetic remodeling in LNCaP and PC3 cell lines
Abstract
Arsenic trioxide (As2O3) is a well-known anticancer drug and is approved by the FDA for its use in acute promyelocytic leukemia. In this study, anticancer and antiproliferative mechanism of biocompatible As2O3 nanoparticles was determined on human prostate cancer cell lines. In vitro anticancer efficacy of biopolymer coated As2O3 NPs was investigated in LNCaP and PC-3 cell lines, by assessing DNA damage, changes in epigenetic modulations, expression level of apoptotic markers and cell cycle analysis following treatment with As2O3 NPs. Our results demonstrate that the nanoparticulate formulation of dimercaptosuccinic acid (DMSA) and chitosan coated As2O3 is capable of inducing morphological changes, DNA damage and caspase-dependent apoptosis along with the expression of cyclin-dependent kinase inhibitor p21 by upregulation of Bax and downregulation of Bcl-2 and Bcl-xL proteins. The expression of cyclin-dependent kinase inhibitor - p21 was found to be triggered by changes in epigenetic modifications at histone tails. Biopolymer coated As2O3 nanoparticles induced reversal of mono, di and tri-methylation of histone H3 at lysine 9 residue. Acetylation of histone H3 at lysine 14 residue and phosphorylation of H3 at serine 10 residue ...Continue Reading
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