Browse

Sulindac induces apoptotic cell death in susceptible human breast cancer cells through, at least in part, inhibition of IKKβ

Cited 12 time in Web of Science Cited 12 time in Scopus
Authors
Seo, A-Mi; Hong, Seung-Woo; Shin, Jae-Sik; Park, In-Chul; Kim, Dae-Jin; Lee, Wang-Jae; Lee, Myeong-Sok; Jin, Dong-Hoon; Lee, Won-Keun; Hong, Nam-Joo
Issue Date
2009-07
Publisher
SPRINGER
Citation
APOPTOSIS; Vol.14, No.7; 913-922
Keywords
NSAIDsApoptosisP38/MAPKJNK1IKK betaSulindac
Abstract
Sulindac is a non-steroidal anti-inflammatory agent with anti-tumor activities that include the induction of apoptosis in various cancer cells and the inhibition malignant transformation. However, the molecular mechanisms underlying these effects are unclear. Recently, it has been shown that sulindac can inhibit NF-kappa B activation. Here, we demonstrate that sulindac induces apoptotic cell death in susceptible human breast cancer cells through, at least in part, inhibition of IKK beta activity. More specifically, when we compared two different human breast cancer cell lines, Hs578T, which has relatively low basal IKKb activity, and MDA-MB231, which has relatively high basal IKKb activity, we found that MDA-MB231 was markedly more sensitive to sulindac-induced apoptosis than Hs578T. This was associated with greater caspase-3 and -9 activity in sulindac-treated MDA-MB231 cells. Using a combination of chemical kinase inhibitors and siRNA-mediated knockdown of specific kinases, we found that sulindac inhibits IKK beta, which, in turn, leads to the p38 MAPK-dependent activation of JNK1. Together, these findings suggest that sulindac induces apoptosis in susceptible human breast cancer cells through, at least in part, the inhibition of IKK beta and the subsequent p38 MAPK-dependent activation of JNK1.
ISSN
1360-8185
Language
English
URI
https://hdl.handle.net/10371/78673
DOI
https://doi.org/10.1007/s10495-009-0367-1
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Anatomy (해부학전공)Journal Papers (저널논문_해부학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse