Constitutive activation of I kappa B kinase alpha and NF-kappa B in prostate cancer cells is inhibited by ibuprofen

Apoptotic pathways controlled by the Rel/NF-kappa B family of transcription factors may regulate the response of cells to DNA damage. Here, we have ex amined the NF-kappa B status Of several prostate tumor cell lines. In the a ndrogen-independent prostate tumor cells PC-3 and DU-145, the DNA-binding a ctivity of NF-kappa B was constitutively activated and I kappa B-alpha leve ls were decreased, In contrast, the androgen-sensitive prostate tumor cell line LNCaP had low levels of NF-kappa B which were upregulated following ex posure to cytokines or DNA damage, The activity of the I kappa B-alpha kina se, IKK alpha, which mediates NF-kappa B activation, was also measured. In PC-3 cells, IKK alpha activity was constitutively active, whereas LNCaP cel ls had minimal IKK alpha activity that was activated by cytokines. The anti -inflammatory agent ibuprofen inhibited the constitutive activation of NF-k appa B and IKK alpha in PC-3 and DU-145 cells, and blocked stimulated activ ation of NF-kappa B in LNCaP cells. However, ibuprofen did not directly inh ibit I kappa B-alpha kinase, The results demonstrate that NF-kappa B is con stitutively activated in the hormone-insensitive prostate tumor cell lines PC-3 and DU-145, but not in the hormone responsive LNCaP cell line. The con stitutive activation of NF-kappa B in prostate tumor cells may increase exp ression of anti-apoptotic proteins, thereby decreasing the effectiveness of anti-tumor therapy and contributing to the development of the malignant ph enotype.