کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2550734 1560580 2016 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Biocompatible arsenic trioxide nanoparticles induce cell cycle arrest by p21WAF1/CIP1 expression via epigenetic remodeling in LNCaP and PC3 cell lines
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Biocompatible arsenic trioxide nanoparticles induce cell cycle arrest by p21WAF1/CIP1 expression via epigenetic remodeling in LNCaP and PC3 cell lines
چکیده انگلیسی

AimsArsenic 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.Main methodsIn 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.Key findingsOur 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.SignificanceBiopolymer 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 synergistically activated p21WAF1/CIP1 gene thereby leading to apoptosis in the LNCaP and PC-3 cells. Treatment with As2O3 nanoparticles arrested the cells in G0-G1 and G2-M phase of cell cycle in LNCaP and PC-3 cells respectively. Thus, biocompatible As2O3 nanoparticles with reduced toxicity to normal cells but the antiproliferative effect on prostate cancer cell lines follow similar death pathway as that of bare As2O3 nanoparticles.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 148, 1 March 2016, Pages 41–52
نویسندگان
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