effect of 5'-fluoro-2'-deoxycytidine, 5-azacytidine, and 5-aza-2'–deoxycytidine on dna methyltransferase 1, cip/kip family, and ink4a/arf in colon cancer hct-116 cell line

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.