5-Azacytidine (5-aza) Induces p53-associated Cell Death Through Inhibition of DNA Methyltransferase Activity in Hep3B and HT-29 Cells

Abstract

Background/aim: DNA methylation regulates the expression of genes that control mechanisms of cell death. TP53 gene expression inhibits tumorigenesis, and its action is closely associated with cell death. 5-Azacytidine (5-aza), increases the expression of the TP53 gene by inhibiting DNA methyltransferase.

Materials and methods: Using 5-aza, we induced DNA hypomethylation in p53-null and p53-expressing cancer cell lines and investigated potential mechanisms of cancer cell death.

Results: TP53 expression promoted cell death. Notably, methylation-specific PCR (MSP) and bisulfite sequencing revealed more methylation sites at the TP53 promoter region in p53-null cells than in p53-expressing cells.

Conclusion: This study suggests a novel mechanism of tumorigenesis regulated by p53 expression.

Keywords: 5-azacytidine; Cancer; Cell death; DNA methylation; p53.