Abstract 1591: Capsaicin enhances the effect of radiation in prostate cancer through NFκB suppression.

Abstract Introduction and Objective: Radio-sensitizing agents sensitize cells to the lethal effects of ionizing radiation (IR). This permits use of lower doses of radiation to achieve equivalent cancer control thereby minimizing adverse effects to normal tissues. Given their lack of toxicity compounds occurring naturally in the diet make ideal potential radio-sensitizing agents. Capsaicin is the active compound chilli peppers. Traditionally capsaicin is used to treat chronic pain syndromes; however, recently evidence using in vitro prostate cancer (PCa) models describes its anti-carcinogenic potential. In our studies we have demonstrated that capsaicin can enhance the effect of radiation of prostate cancer in vitro and in vivo. The objective of the present study is to assess the how capsaicin enhances the effect of radiation in vitro an in vivo models. Methods: Using clonogenic assays we assessed the effect of ionizing radiation (1-8 Gy) and/or capsaicin (1-10μM) on colony formation rates in 4 human PCa cell lines (LNCaP, PC3, PC3AR2, DU145). Western Blot and immunocytochemical analysis was performed to examine mechanistic changes. Athymic nude mice were inoculated subcutaneously with human PCa (LNCaP) cells. Once xenografts reach 100mm3 forty animals will be randomized into 4 groups (15 /group); control (no treatment), capsaicin alone, ionizing radiation (IR) alone and capsaicin and IR. Treatments were administered over a two-week time period. Capsaicin (5 mg/kg/d) or vehicle was administered 3/week by gavage. RT will be delivered to animals in sterile cages as one fraction (6 Gray). Tumours were measured thrice weekly and volumes were calculated. Tumours were fixed and stained for pathological analyses and immunohistochemical evaluation. Results: Exposure of cells to capsaicin (1-10μM) or IR (1-8Gy) caused significant dose-dependent inhibition of colony formation (p<0.001). Combining capsaicin with IR resulted in further significant inhibition of colony formation rates (P<0.001). Western Blot and IHC analysis showed that LNCaP cells treated with capsaicin and/or IR suppressed AR and NFκB, and increase DNA damage. Mice treated with capsaicin or IR alone had a significant reduction in tumour growth overtime (p < 0.001). Mice treated with capsaicin and IR capsaicin had a reduction in the tumour volume greater than either capsaicin alone (p<0.001) or radiation alone (p<0.03). Two mice experienced mild to moderate inflammation of the stomach. No other toxicities were observed. Mechanistic studies revealed that mice administered capsaicin and radiation had an increased yH2AX expression, and significantly lower Ki67 index, AR, and NFκB expression. Conclusion: These studies suggest that capsaicin enhances the effect of radiation through a number of mechanisms including the suppression of NFκB and AR. Citation Format: Natalie A. Venier, Alexandra J. Colquhoun, Laurence Klotz, Neil Fleshner, Vasundara Venkateswaran. Capsaicin enhances the effect of radiation in prostate cancer through NFκB suppression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1591. doi:10.1158/1538-7445.AM2013-1591