Enhancement of radiosensitivity by a unique novel NF-κB inhibitor, DHMEQ, in prostate cancer

BACKGROUND: Inducible activation of nuclear factor (NF)-kappa B is one of the principal mechanisms through which resistant prostate cancer cells are protected from radiotherapy. We hypothesised that inactivation of inducible NF-kappa B with a novel NF-kappa B inhibitor, DHMEQ, would increase the therapeutic effects of radiotherapy. METHODS: PC-3 and LNCaP cells were exposed to irradiation and/or DHMEQ. Cell viability, cell cycle analysis, western blotting assay, and NF-kappa B activity were measured. The antitumour effect of irradiation combined with DHMEQ in vivo was also assessed. RESULTS: The combination of DHMEQ with irradiation resulted in cell growth inhibition and G2/M arrest relative to treatment with irradiation alone. Inducible NF-kappa B activity by irradiation was inhibited by DHMEQ treatment. The expression of p53 and p21 in LNCaP, and of 14-3-3 sigma in PC-3 cells, was increased in the combination treatment. In the in vivo study, 64 days after the start of treatment, tumour size was 85.1%, 77.1%, and 64.7% smaller in the combination treatment group than that of the untreated control, DHMEQ-treated alone, and irradiation alone groups, respectively. CONCLUSION: Blockade of NF-kappa B activity induced by radiation with DHMEQ could overcome radio-resistant responses and may become a new therapeutic modality for treating prostate cancer. British Journal of Cancer (2012) 104, 652-657. doi:10.1038/bjc.2012.321 www.bjcancer.com Published online 17 July 2012 (C) 2012 Cancer Research UK