DNA methyltransferase 1 inhibits O6-methylguanine-DNAmethyl-transferase-mediated cell growth and metastasis of hypopharyngeal squamous carcinoma

2021 ◽  
pp. 105160
Author(s):  
Ruxian Tian ◽  
Yayun Lv ◽  
Xin Yang ◽  
Limei Cui ◽  
Xinxin Wu ◽  
...  
Author(s):  
Masumeh Sanaei ◽  
Fraidoon Kavoosi

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.


2022 ◽  
Vol 14 (12) ◽  
Author(s):  
Masumeh Sanaei ◽  
Fraidoon Kavoosi

Background: Cyclin-dependent kinase inhibitors (CKIs) are the negative regulator of cell cycle progression, which inhibits cyclin-cdk complexes, resulting in cell cycle arrest. Recently, we evaluated the effect of 5-Aza-CdR on DNMT1 gene expression in the WCH-17 hepatocellular carcinoma (HCC) cell line. Objectives: The current study was designed to analyze the effects of 5-aza-2'–deoxycytidine (5-Aza-CdR, decitabine), 5-azacytidine (5-AzaC, vidaza), and 5'-fluoro-2'-deoxycytidine (FdCyd) on INK4a/ARF, CIP/KIP, and DNA methyltransferase 1 gene expression, apoptosis induction, and cell growth inhibition in colon cancer HCT-116 cell line. Methods: The colon cancer HCT-116 cell line was treated with 5-azaC, 5-Aza-CdR, and FdCyd at 24 and 48h. To determine colon cancer HCT-116 cell viability, cell apoptosis, and the relative expression level of the INK4a/ARF, CIP/KIP, and DNA methyltransferase 1 genes, MTT assay, flow cytometry, and qRT-PCR were done, respectively. Results: 5-azaC, 5-Aza-CdR, and FdCyd significantly inhibited colon cancer HCT-116 cell growth and induced apoptosis. Besides, they significantly increased CIP/KIP (p21CIP1, p27KIP1, and p57KIP2) and INK4 (p14ARF, p15INK4b, and p16INK4a) and decreased DNMT1 gene expression. Besides, minimal and maximal apoptosis were seen in the groups treated with FdCyd and 5-Aza-CdR, respectively. The IC50 for CAF for FdCyd was 1.72 ± 0.23 and 1.63 ± 0.21μM at 24 and 48h, respectively. The IC50 for CAF for 5-AzaC was 2.18 ± 0.33 and 1.98 ± 0.29 μM at 24 and 48h, respectively. The IC50 for CAF for 5-Aza-CdR was 4.08 ± 0.61 and 3.18 ± 0.50 μM at 24 and 48h, respectively. Conclusions: The 5-azac, 5-Aza-CdR, and FdCyd can reactivate the INK4a/ARF and CIP/KIP families through inhibition of DNMT1 activity.


2011 ◽  
Vol 108 (9) ◽  
pp. 3630-3635 ◽  
Author(s):  
Lisa S. Shock ◽  
Prashant V. Thakkar ◽  
Erica J. Peterson ◽  
Richard G. Moran ◽  
Shirley M. Taylor

Epigenetics ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. 944-952 ◽  
Author(s):  
Bernardo J Krause ◽  
Paula M Costello ◽  
Ernesto Muñoz-Urrutia ◽  
Karen A Lillycrop ◽  
Mark A Hanson ◽  
...  

2016 ◽  
Vol 36 (22) ◽  
pp. 6050-6068 ◽  
Author(s):  
Hirofumi Noguchi ◽  
Naoya Murao ◽  
Ayaka Kimura ◽  
Taito Matsuda ◽  
Masakazu Namihira ◽  
...  

Biochimie ◽  
2014 ◽  
Vol 106 ◽  
pp. 149-156 ◽  
Author(s):  
Cheng-gui Miao ◽  
Ying-ying Yang ◽  
Xu He ◽  
Cheng Huang ◽  
Yan Huang ◽  
...  

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