The Effect of 5-aza,2'-deoxyCytidine (5 AZA CdR or Decitabine) on Extrinsic, Intrinsic, and JAK/STAT Pathways in Neuroblastoma and Glioblastoma Cells Lines

Epigenetic changes such as histone deacetylation and DNA methylation play to regulate gene expression. DNA methylation plays a major role in cancer induction via transcriptional silencing of critical regulators such as tumor suppressor genes (TSGs). One approach to inhibit TSGs inactivation is to use chemical compounds, DNA methyltransferase inhibitors (DNMTIs). Previously, we investigated the effect of 5-aza-2'-deoxycytidine (5 AZA CdR or decitabine) on colon cancer and hepatocellular carcinoma cell lines. The present study aimed to investigate the effect of 5 AZA CdR on extrinsic (DR4, DR5, FAS, FAS-L, and TRAIL genes), intrinsic [pro- (Bax, Bak, and Bim) and anti- (Bcl-2, Bcl-xL, and Mcl-1) apoptotic genes], and JAK/STAT (SOCS1, SOCS3, JAK1, JAK2, STAT3, STAT5A, and STAT5B genes) pathways in neuroblastoma (IMR-32, SK-N-AS, UKF-NB-2, UKF-NB-3, and UKF-NB-4) and glioblastoma (SF-767, SF-763, A-172, U-87 MG, and U-251 MG) cell lines. The neuroblastoma and glioblastoma cells were cultured and treated with 5 AZA CdR. To determine cell viability, cell apoptosis, and the relative gene expression level, MTT assay, flow cytometry assay, and qRT-PCR were done respectively. 5 AZA CdR changed the expression level of the genes of the extrinsic, intrinsic, and JAK/STAT pathways by which induced cell apoptosis and inhibited cell growth in neuroblastoma and glioblastoma cell lines. 5 AZA CdR can play its role through extrinsic, intrinsic, and JAK/STAT pathways to induce cell apoptosis.