5‐Azacytidine specifically inhibits the NIH‐3T3 PCD process induced by TNF‐alpha and cycloheximide via affecting BCL‐XL. Issue 2 (28th August 2017)

• Record Type: Journal Article
• Authors: Wang, Qing; Wang, Pu; Zhou, Hong; Hu, Yan; Xie, Chengshen; Gao, Fei; Ma, Ningjie; Hou, Haoli; Zhang, Hao; Li, Lijia
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 2(2018)
• Page Start: 1501
• Page End: 1510
• Publication Date: 2017-08-28
• Subjects: 5‐azacytidine -- apoptosis -- BCL‐2 family -- DNA methylation -- TNF‐α and Cycloheximide; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26310
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: DNA methylation plays a crucial role in lots of biological processes and cancer. 5‐azacytidine (5‐AC), a DNA methylation inhibitor, has been used as a potential chemotherapeutic agent for cancer. In this study, we used 5‐AC treatment to investigate whether DNA methylation was involved in regulation of programmed cell death (PCD) in mouse embryo fibroblast NIH‐3T3 cells which could undergo PCD after treatment with TNF‐α and cycloheximide (CHX). The results showed that the genomic DNA of NIH‐3T3 cells was hypermethylated during PCD induced by TNF‐α and CHX, and 5‐AC might prevent this PCD process. However, treatment with the other three DNA methylation inhibitors, 5‐aza‐deoxycytidine, 6‐thioguanine and RG108, did not interfere with the NIH‐3T3 cell PCD process. Additionally, knockdown of DNMT1 did not affect the apoptosis process. The present results and observations indicated that 5‐AC specifically inhibited the NIH‐3T3 apoptosis process via a genomic DNA methylation‐independent pathway. During the TNF‐α and CHX‐inducing apoptosis process, the PCD related BCL‐2 family proteins were significantly down‐regulated. Furthermore, after the small interference RNA‐mediated knockdown of BCL‐XL, one of the BCL‐2 family proteins, 5‐AC did not inhibit the apoptosis process, suggesting that 5‐AC inhibited the PCD process induced by TNF‐α and CHX by affecting the anti‐apoptotic protein BCL‐XL. Abstract : DNA methylation inhibitor 5‐azacytidine specifically inhibited NIH‐3T3 cell apoptosis induced by TNF‐α and CHX via a genomic DNA methylation‐independent pathway. While after the small interference RNA mediated knockdown of BCL‐XL, one of the BCL‐2 family proteins, 5‐AC could not inhibit the apoptosis process, suggesting that 5‐AC inhibited the PCD process through affecting the anti‐apoptotic protein BCL‐XL.