标题:Chaetocin induces endoplasmic reticulum stress response and leads to death receptor 5-dependent apoptosis in human non-small cell lung cancer cells
作者:Liu, Xianfang;Guo, Sen;Liu, Xiangguo;Su, Ling
作者机构:[Liu, X] Shandong University School of Life Sciences, Rm103, South Bldg, 27 Shanda South RD, Jinan, 250100, China, Department of Otolaryngology Head a 更多
通讯作者:Su, L
通讯作者地址:[Su, L]Shandong Univ, Sch Life Sci, Rm103,South Bldg,27 Shanda South RD, Jinan 250100, Peoples R China.
来源:Apoptosis: An international journal on programmed cell death
出版年:2015
卷:20
期:11
页码:1499-1507
DOI:10.1007/s10495-015-1167-4
关键词:Chaetocin;SUV39H1;CHOP;ATF3;DR5;Apoptosis
摘要:Epigenetic abnormalities are associated with non-small cell lung cancer (NSCLC) initiation and progression. Epigenetic drugs are being studied and in clinical trials. However, the molecular mechanism underlying the apoptosis by the epigenetic agents remains unclear. SUV39H1 is an important methyl-transferase for lysine 9 on histone H3 and usually related to gene transcriptional suppression, and chaetocin acts as the inhibitor of SUV39H1. We demonstrated here that chaetocin effectively suppressed the growth of multiple lung cancer cells through inducing apoptosis in a death receptor 5 (DR5)-dependent manner. Chaetocin treatment activated endoplasmic reticulum (ER) stress which gave rise to the up-regulation of ATF3 and CHOP. Furthermore, ATF3 and CHOP contributed to the induction of DR5 and subsequent apoptosis. When SUV39H1 was silenced with siRNA, the expression of ATF3, CHOP and DR5 was elevated. Thereafter, knockdown of SUV39H1 induced apoptosis in NSCLC cells. In summary, chaetocin pharmacologically inhibits the activity of SUV39H1 which provokes ER stress and results in up-regulation of ATF3 and CHOP, leading to DR5-dependent apoptosis eventually. These findings provide a novel interpretation on the anti-neoplastic activity of epigenetic drugs as a new therapeutic approach in NSCLC.
收录类别:SCOPUS;SCIE
WOS核心被引频次:12
Scopus被引频次:13
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84942550534&doi=10.1007%2fs10495-015-1167-4&partnerID=40&md5=055f37026a4adf5f3ac5b85bf8812ace
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