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5‐Azacytidine specifically inhibits the NIH‐3T3 PCD process induced by TNF‐alpha and cycloheximide via affecting BCL‐XL
Author(s) -
Wang Qing,
Wang Pu,
Zhou Hong,
Hu Yan,
Xie Chengshen,
Gao Fei,
Ma Ningjie,
Hou Haoli,
Zhang Hao,
Li Lijia
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26310
Subject(s) - cycloheximide , apoptosis , gene knockdown , programmed cell death , dna methylation , methylation , microbiology and biotechnology , biology , cancer research , chemistry , dna , protein biosynthesis , biochemistry , gene expression , gene
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.