期刊
APOPTOSIS
卷 13, 期 11, 页码 1378-1385出版社
SPRINGER
DOI: 10.1007/s10495-008-0264-z
关键词
Rottlerin; Endoplasmic reticulum stress; Apoptosis; CHOP; Unfolded protein response
资金
- KOSEF [M1075604000107N560400110]
- Keimyung University [R13-2002-028-01002-0]
- Korean Government (MOEHRD) [KRF-2007-355-C00050]
- Korea Research Foundation [KRF-2005-070-C00100]
- National Research Foundation of Korea [2005-070-C00100] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Rottlerin, a compound reported to be a PKC delta-selective inhibitor, has been shown to induce growth arrest or apoptosis of human cancer cell lines. In our study, rottlerin dose-dependently induced apoptotic cell death in colon carcinoma cells. Treatment of HT29 human colon carcinoma cells with rottlerin was found to induce a number of signature ER stress markers; phosphorylation of eukaryotic initiation factor-2 alpha (eIF-2 alpha), ER stress-specific XBP1 splicing, and up-regulation of glucose-regulated protein (GRP)-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP). However, suppression of PKC delta expression by siRNA or overexpression of WT-PKC delta and DN-PKC delta did not abrogate the rottlerin-mediated induction of CHOP. These results suggest that rottlerin induces up-regulation of CHOP via PKC delta-independent pathway. Furthermore, down-regulation of CHOP expression using CHOP siRNA attenuated rottlerin-induced apoptosis. Taken together, the present study thus provides strong evidence to support an important role of ER stress response in mediating the rottlerin-induced apoptosis.
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