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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.

galen medical journal

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