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

• Published in: Anticancer research Vol. 43; no. 2; pp. 639 - 644
• Main Authors: Kim, Dae-Yeon, Lee, Rangyeon, Cheong, Hee-Tae, Ra, Chang-Six, Rhee, Ki-Jong, Park, Jeongho, Jung, Bae Dong
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.02.2023
• Subjects: Azacitidine - pharmacology; Azacytidine; Bisulfite; Cancer; Carcinogenesis - genetics; Cell Death; Cell Line, Tumor; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA Methylation; DNA methyltransferase; DNA Modification Methylases - genetics; Gene expression; Genes, p53; HT29 Cells; Humans; Mortality; Null cells; p53 Protein; Tumor cell lines; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumorigenesis; 5-azacytidine; DNA methylation; Cell death; Cancer; p53
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.16200

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. Using 5-aza, we induced DNA hypomethylation in p53-null and p53-expressing cancer cell lines and investigated potential mechanisms of cancer cell death. 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. This study suggests a novel mechanism of tumorigenesis regulated by p53 expression.