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 journalArticle

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
StatePublished - Dec 2 1999
Externally publishedYes

Fingerprint

Ibuprofen
Prostatic Neoplasms
Phosphotransferases
Prostate
Tumor Cell Line
Androgens
DNA Damage
Hormones
Cytokines
Neoplasms
Apoptosis Regulatory Proteins
Anti-Inflammatory Agents
Transcription Factors
Phenotype
Cell Line
DNA

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Palayoor, S. T., Youmell, M. Y., Calderwood, S. K., Coleman, C. N., & Price, B. D. (1999). Constitutive activation of IκB kinase α and NF-κB in prostate cancer cells is inhibited by ibuprofen. Oncogene, 18(51), 7389-7394.

Constitutive activation of IκB kinase α and NF-κB in prostate cancer cells is inhibited by ibuprofen. / Palayoor, S. T.; Youmell, M. Y.; Calderwood, S. K.; Coleman, C. N.; Price, B. D.

In: Oncogene, Vol. 18, No. 51, 02.12.1999, p. 7389-7394.

Research output: Contribution to journalArticle

Palayoor, ST, Youmell, MY, Calderwood, SK, Coleman, CN & Price, BD 1999, 'Constitutive activation of IκB kinase α and NF-κB in prostate cancer cells is inhibited by ibuprofen', Oncogene, vol. 18, no. 51, pp. 7389-7394.
Palayoor ST, Youmell MY, Calderwood SK, Coleman CN, Price BD. Constitutive activation of IκB kinase α and NF-κB in prostate cancer cells is inhibited by ibuprofen. Oncogene. 1999 Dec 2;18(51):7389-7394.
Palayoor, S. T. ; Youmell, M. Y. ; Calderwood, S. K. ; Coleman, C. N. ; Price, B. D. / Constitutive activation of IκB kinase α and NF-κB in prostate cancer cells is inhibited by ibuprofen. In: Oncogene. 1999 ; Vol. 18, No. 51. pp. 7389-7394.
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