Arsenic Trioxide Induces Cell Cycle Arrest and Alters Dna Methylation Patterns of Cell Cycle Regulatory Genes in Colorectal Cancer Cells

Arsenic Trioxide Induces Cell Cycle Arrest and Alters Dna Methylation Patterns of Cell Cycle Regulatory Genes in Colorectal Cancer Cells Publisher Pubmed

Eyvani H¹ ; Moghaddaskho F¹ ; Kabuli M² ; Zekri A³ ; Momeny M¹ ; Tavakkolybazzaz J² ; Alimoghaddam K¹ ; Ghavamzadeh A¹ ; Ghaffari SH¹

Show Affiliations

1. Hematology Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
3. Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

Source: Life Sciences Published:2016

Abstract

Aims Cell cycle dysregulation is important in tumorigenesis. Transcriptional silencing of cell cycle regulatory genes, due to DNA methylation, is a common epigenetic event in malignancies. As2O3 has been shown to induce cell cycle arrest and also to be a potential hypomethylating agent. Our study aimed to investigate DNA methylation patterns of cell cycle regulatory genes promoters, the effects of Arsenic trioxide (As2O3) on the methylated genes and cell cycle distribution in colorectal cancer (CRC) cell lines. Main methods The methylation-specific PCR (MSP) and/or restriction enzyme-based methods were used to study the promoter methylation patterns of 24 cell cycle regulatory genes in CRC cell lines. Gene expression level and cell cycle distribution were determined by Real-time PCR and flow cytometric analyses, respectively. Key findings Our methylation analysis indicated that only promoters of RBL1 (p107), CHFR and p16 genes were aberrantly methylated in three cell lines. As2O3 significantly decreased DNA methylation in promoter regions of these genes and restored their expression. We found that As2O3 significantly reduced the expression of DNA methyltransferase 1 (DNMT1) and increased arsenic methyltransferase (AS3MT). Furthermore, As2O3 altered transcriptional activity of several unmethylated cell cycle regulatory genes including cyclin B1, E1, D1, GADD45A and p21. Cell cycle flow cytometry analysis showed As2O3 induced G2/M arrest in all three cell lines. Significance These data suggest that demethylation and alteration in the expression level of the cell cycle-related genes may be possible mechanisms in As2O3-induced cell cycle arrest in colorectal cancer cells. © 2016 Elsevier Inc.

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Style	Citing Format
MLA	Eyvani H, et al.. "Arsenic Trioxide Induces Cell Cycle Arrest and Alters Dna Methylation Patterns of Cell Cycle Regulatory Genes in Colorectal Cancer Cells." Life Sciences, vol. 167, no. , 2016, pp. 67-77.
APA	Eyvani H, Moghaddaskho F, Kabuli M, Zekri A, Momeny M, Tavakkolybazzaz J, Alimoghaddam K, Ghavamzadeh A, Ghaffari SH (2016). Arsenic Trioxide Induces Cell Cycle Arrest and Alters Dna Methylation Patterns of Cell Cycle Regulatory Genes in Colorectal Cancer Cells. Life Sciences, 167(), 67-77.
Chicago	Eyvani H, Moghaddaskho F, Kabuli M, Zekri A, Momeny M, Tavakkolybazzaz J, Alimoghaddam K, Ghavamzadeh A, Ghaffari SH. "Arsenic Trioxide Induces Cell Cycle Arrest and Alters Dna Methylation Patterns of Cell Cycle Regulatory Genes in Colorectal Cancer Cells." Life Sciences 167, no. (2016): 67-77.
Harvard	Eyvani H et al. (2016) 'Arsenic Trioxide Induces Cell Cycle Arrest and Alters Dna Methylation Patterns of Cell Cycle Regulatory Genes in Colorectal Cancer Cells', Life Sciences, 167(), pp. 67-77.
Vancouver	Eyvani H, Moghaddaskho F, Kabuli M, Zekri A, Momeny M, Tavakkolybazzaz J, et al.. Arsenic Trioxide Induces Cell Cycle Arrest and Alters Dna Methylation Patterns of Cell Cycle Regulatory Genes in Colorectal Cancer Cells. Life Sciences. 2016;167():67-77.
BibTex	@article{ author = {Eyvani H and Moghaddaskho F and Kabuli M and Zekri A and Momeny M and Tavakkolybazzaz J and Alimoghaddam K and Ghavamzadeh A and Ghaffari SH}, title = {Arsenic Trioxide Induces Cell Cycle Arrest and Alters Dna Methylation Patterns of Cell Cycle Regulatory Genes in Colorectal Cancer Cells}, journal = {Life Sciences}, volume = {167}, number = {}, pages = {67-77}, year = {2016} }
RIS	TY - JOUR AU - Eyvani H AU - Moghaddaskho F AU - Kabuli M AU - Zekri A AU - Momeny M AU - Tavakkolybazzaz J AU - Alimoghaddam K AU - Ghavamzadeh A AU - Ghaffari SH TI - Arsenic Trioxide Induces Cell Cycle Arrest and Alters Dna Methylation Patterns of Cell Cycle Regulatory Genes in Colorectal Cancer Cells JO - Life Sciences VL - 167 IS - SP - 67 EP - 77 PY - 2016 ER -

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