Constitutive activation of IκB kinase α and NF-κB in prostate cancer cells is inhibited by ibuprofen

S. T. Palayoor, M. Y. Youmell, S. K. Calderwood, C. N. Coleman, B. D. Price

Research output: Contribution to journalArticlepeer-review

Abstract

Apoptotic pathways controlled by the Rel/NF-κB family of transcription factors may regulate the response of cells to DNA damage. Here, we have examined the NF-κB status of several prostate tumor cell lines. In the androgen-independent prostate tumor cells PC-3 and DU-145, the DNA-binding activity of NF-κB was constitutively activated and IκB-α levels were decreased. In contrast, the androgen-sensitive prostate tumor cell line LNCaP had low levels of NF-κB which were upregulated following exposure to cytokines or DNA damage. The activity of the IκB-α kinase, IKKα, which mediates NF-κB activation, was also measured. In PC-3 cells, IKKα activity was constitutively active, whereas LNCaP cells had minimal IKKα activity that was activated by cytokines. The anti-inflammatory agent ibuprofen inhibited the constitutive activation of NF-κB and IKKα in PC-3 and DU-145 cells, and blocked stimulated activation of NF-κB in LNCaP cells. However, ibuprofen did not directly inhibit IκB-α kinase. The results demonstrate that NF-κB is constitutively activated in the hormone-insensitive prostate tumor cell lines PC-3 and DU-145, but not in the hormone responsive LNCaP cell line. The constitutive activation of NF-κB in prostate tumor cells may increase expression of anti-apoptotic proteins, thereby decreasing the effectiveness of anti-tumor therapy and contributing to the development of the malignant phenotype.

Original languageEnglish (US)
Pages (from-to)7389-7394
Number of pages6
JournalOncogene
Volume18
Issue number51
DOIs
StatePublished - Dec 2 1999

Keywords

  • Androgen
  • IKKα
  • Ibuprofen
  • NF-κB
  • Prostate
  • Tumor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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