scholarly journals Effect of 5-aza-2'-deoxycytidine in comparison to valproic acid and trichostatin a on histone deacetylase 1, dna methyltransferase 1, and cip/kip family (p21, p27, and p57) genes expression, cell growth inhibition, and apoptosis induction in colon cancer sw480 cell line

2019 ◽  
Vol 8 (1) ◽  
pp. 52 ◽  
Author(s):  
Fraidoon Kavoosi ◽  
Masumeh Sanaei
Keyword(s):  
Valproic Acid ◽  
Dna Methyltransferase ◽  
Trichostatin A ◽  
Sw480 Cell ◽  
Dna Methyltransferase 1 ◽  
Apoptosis Induction ◽  
Cell Growth Inhibition ◽  
Histone Deacetylase 1 ◽  
Sw480 Cell Line ◽  
Genes Expression

Effect of 5-fluoro-2′-deoxycytidine (FdCyd) on p16INK4a, p14ARF, p15INK4b, and DNA methyltransferase 1, 3a, and 3b Genes Expression, Apoptosis Induction, and Cell Growth Inhibition in Pancreatic Cancer AsPC-1 and Hepatocellular Carcinoma LCL-PI 11 Cell Li

2020 ◽  
Author(s):  
Masumeh Sanaei ◽  
Fraidoon Kavoosi
Keyword(s):  
Cell Growth ◽  
Growth Inhibition ◽  
Cell Apoptosis ◽  
Dna Methyltransferase ◽  
Dna Methyltransferase 1 ◽  
Dependent Manner ◽  
Apoptosis Induction ◽  
Cell Growth Inhibition ◽  
Genes Expression ◽  
Methyltransferase 1

Background: Aberrant DNA methylation of the promoter region is one of the most epigenetic changes in numerous cancers. DNA methyltransferase inhibitors (DNMTIs) can revert DNA hypermethylation in tumor suppressor genes (TSGs). The present study was designed to investigate the effect of 5-fluoro-2′-deoxycytidine (FdCyd) on p16INK4a, p14ARF, p15INK4b, and DNA methyltransferase 1, 3a, and 3b genes expression, apoptosis induction, cell growth inhibition in pancreatic cancer AsPC-1 and hepatocellular carcinoma LCL-PI 11 cell lines. Materials and Methods: The cells were treated with FdCyd at different periods. Then, the MTT assay, cell apoptosis assay, and qRT-PCR were done to determine cell viability, cell apoptosis, and the relative gene expression level respectively. Results: The FdCyd decreased DNA methyltransferase 1, 3a, and 3b and increased p16INK4a, p14ARF, and p15INK4b genes expression significantly (P<0.001). Besides, LCL-PI 11 cell was more sensitive to FdCyd in comparison to AsPC-1 cell. FdCyd induced significant cell growth inhibition with a dose- and time-dependent manner (P<0.001). The IC50 value of FdCyd was obtained with approximately 1μM. Further, FdCyd induced cell apoptosis significantly as a time-dependent manner. The number of apoptotic cells was significantly increased in all groups. The percentage of apoptotic cells after 24 and 48 h were 13.86 and 29.6 % in AsPC-1 and 21.04 and 41.52 % in LCL-PI 11 cell line respectively (P<0.001). Conclusion: The FdCyd can reactivate the p16INK4a, p14ARF, and p15INK4b through inhibition of DNA methyltransferase 1, 3a, and 3b gene expression.

scholarly journals Effect of 5-aza-2ˈ-deoxycytidine on p27Kip1, p21Cip1/Waf1/Sdi1, p57Kip2, and DNA methyltransferase 1 Genes Expression, Cell Growth Inhibition and Apoptosis Induction in Colon Cancer SW 480 and SW 948 Cell Lines

2020 ◽  
Vol 9 ◽  
pp. 1899
Author(s):  
Masumeh Sanaei ◽  
Fraidoon Kavoosi ◽  
Sedighe Nasiri
Keyword(s):  
Colon Cancer ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Cell Line ◽  
Cell Lines ◽  
Dna Methyltransferase ◽  
Dna Methyltransferase 1 ◽  
Apoptosis Induction ◽  
Cell Growth Inhibition ◽  
Genes Expression

Background: Dysregulation of the cell cycle has been reported in various cancers. Inactivation of the cyclin-dependent kinases inhibitors (CDKIs), CIP/KIP family, such as p21Cip1/Waf1/Sdi1, p27Kip1, and p57Kip2 genes because of hypermethylation has been shown in several cancers. Treatment with DNA demethylating agent 5-aza-2ˈ-deoxycytidine (5-Aza-CdR) has been indicated that affect genomic methylation and resulting in silenced genes reactivation in colon cancer. Previously, we evaluated the effect of 5-Aza-CdR on DNA methyltransferase 1 (DNMT1) gene expression in hepatocellular carcinoma (HCC) which encouraged us to design the current study. The present study aimed to evaluate the effect of 5-Aza-CdR on p21Cip1/Waf1/Sdi1, p27Kip1, p57Kip2, and DNAT1 genes expression, cell growth inhibition and apoptosis induction in colon cancer SW 480 and SW 948 cell lines. Materials and Methods: The effect of 5-aza-CdR on the SW 480 and SW 948 cells growth, apoptosis induction and genes expression were assessed by MTT assay, flow cytometry, and real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis respectively. Results: 5-aza-CdR inhibited cell growth as time- and dose-dependent manner significantly (P<0.001). The agent reactivated p15INK4, p16INK4, p18INK4, and p19INK4 genes expression and induced apoptosis at a concentration of 5 μM significantly. Besides, 5-aza-CdR had a more significant effect on the SW 480 cell line in comparison to SW 948 cell line. Conclusion: 5-Aza-CdR plays a key role in the up-regulation of p21Cip1/Waf1/Sdi1, p27Kip1, and p57Kip2 and down-regulation of DNMT1 genes resulting in cell growth inhibition and apoptosis induction. [GMJ.2020;9:e1899] DOI:10.31661/gmj.v9i0.1899

scholarly journals Chromium Cross-Links Histone Deacetylase 1-DNA Methyltransferase 1 Complexes to Chromatin, Inhibiting Histone-Remodeling Marks Critical for Transcriptional Activation

2007 ◽  
Vol 27 (20) ◽  
pp. 7089-7101 ◽  
Author(s):  
Michael Schnekenburger ◽  
Glenn Talaska ◽  
Alvaro Puga
Keyword(s):  
Gene Expression ◽  
Histone Deacetylase ◽  
Dna Methyltransferase ◽  
Epigenetic Modification ◽  
Dna Methyltransferase 1 ◽  
Transcriptional Responses ◽  
Histone Deacetylase 1 ◽  
Environmental Agents ◽  
Cross Links ◽  
Methyltransferase 1

ABSTRACT Transcriptional regulation of gene expression requires posttranslational modification of histone proteins, which, in concert with chromatin-remodeling factors, modulate chromatin structure. Exposure to environmental agents may interfere with specific histone modifications and derail normal patterns of gene expression. To test this hypothesis, we coexposed cells to binary mixtures of benzo[a]pyrene (B[a]P), an environmental procarcinogen that activates Cyp1a1 transcriptional responses mediated by the aryl hydrocarbon receptor (AHR), and chromium, a carcinogenic heavy metal that represses B[a]P-inducible AHR-mediated gene expression. We show that chromium cross-links histone deacetylase 1-DNA methyltransferase 1 (HDAC1-DNMT1) complexes to Cyp1a1 promoter chromatin and inhibits histone marks induced by AHR-mediated gene transactivation, including phosphorylation of histone H3 Ser-10, trimethylation of H3 Lys-4, and various acetylation marks in histones H3 and H4. These changes inhibit RNA polymerase II recruitment without affecting the kinetics of AHR DNA binding. HDAC1 and DNMT1 inhibitors or depletion of HDAC1 or DNMT1 with siRNAs blocks chromium-induced transcriptional repression by decreasing the interaction of these proteins with the Cyp1a1 promoter and allowing histone acetylation to proceed. By inhibiting Cyp1a1 expression, chromium stimulates the formation of B[a]P DNA adducts. Epigenetic modification of gene expression patterns may be a key element of the developmental and carcinogenic outcomes of exposure to chromium and to other environmental agents.

EFFECT OF VALPROIC ACID IN COMPARISON WITH VORINOSTAT ON CELL GROWTH INHIBITION AND APOPTOSIS INDUCTION IN THE HUMAN COLON CANCER SW48 CELLS IN VITRO

2018 ◽  
Vol 40 (2) ◽  
pp. 95-100 ◽  
Author(s):  
M Sanaei ◽  
F Kavoosi ◽  
O Mansoori
Keyword(s):  
Colon Cancer ◽  
Valproic Acid ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Histone Deacetylases ◽  
Regulation Of Gene Expression ◽  
Human Colon ◽  
Apoptosis Induction ◽  
Cell Growth Inhibition ◽  
Human Colon Cancer

Aim: Acetylation levels of histones are the result of the balance between histone acetyltransfrases and histone deacetylases activities, which plays an important role in chromatin remodeling and regulation of gene expression. Histone deacetylases inhibitors such as valproic acid, vorinostat have attracted interest because of their ability to induce differentiation and apoptosis of cancer cells. The current study was designed to assess the effect of valproic acid in comparison to and in combination with vorinostat on cell growth inhibition and apoptosis induction in the human colon cancer SW48 cells. Materials and Methods: The colon cancer SW48 cells were seeded and treated with various doses of valproic acid and vorinostat and MTT assay and flow cytometric assay were done to determine cell viability and cell apoptosis, respectively. Results: All concentrations of both agents reduced viability significantly in a dose- and time-dependent fashion (p < 0.004). Both compounds, either single or combined agents, induced apoptosis significantly, whereas the ratio of the apoptotic cells treated with combined agents was more significant than the single. Conclusion: Our findings suggest that vaproic acid and vorinostat can significantly inhibit cell growth and induce apoptosis in colon cancer SW48 cells.

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