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


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-κB activation. Here, we demonstrate that sulindac induces apoptotic cell death in susceptible human breast cancer cells through, at least in part, inhibition of IKKβ activity. More specifically, when we compared two different human breast cancer cell lines, Hs578T, which has relatively low basal IKKβ activity, and MDA-MB231, which has relatively high basal IKKβ 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 IKKβ, 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 IKKβ and the subsequent p38 MAPK-dependent activation of JNK1.

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Non-steroidal anti-inflammatory drugs


IκB kinase β


c-Jun NH2-terminal kinase 1




Matogen-activated protein kinase


Nuclear factor kappa B


Inhibitory kappa B


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Financial support: This research was supported by the Research Center for Women’s Diseases, at the Korea Science and Engineering Foundation (KOSEF) and by a grant from Sookmyung Women’s University.

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Correspondence to Dong-Hoon Jin or Myeong-Sok Lee.

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A-Mi Seo and Seoug-Woo Hong have contributed equally.

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Seo, AM., Hong, SW., Shin, JS. et al. Sulindac induces apoptotic cell death in susceptible human breast cancer cells through, at least in part, inhibition of IKKβ. Apoptosis 14, 913–922 (2009).

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  • NSAIDs
  • Sulindac
  • IKKβ
  • JNK1
  • P38/MAPK
  • Apoptosis