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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, the active compound chilli peppers, has recently been reported to have some anti-carcinogenic potential in vitro. The objective of the present study is to assess the how capsaicin is radio-sensitizing capacity in vitro an in vivo models.
Methods: Using clonogenic assays the effect of IR (1-8 Gy) and/or capsaicin (1-10μM) on colony formation rates was assessed in human PCa cell lines (LNCaP, PC3, PC3AR2, DU145). Western Blot and ICC were performed to look for alterations in AR and NFκB expression. Athymic nude mice were inoculated subcutaneously with human PCa (LNCaP) cells. Once xenografts reached 100mm3 mice were randomized into 4 groups (15 /group); control (no treatment), capsaicin alone (5 mg/kg/d), IR alone (6 Gray) and capsaicin and IR. Treatments were administered over a two-week time period. Tumours were fixed and stained for pathological analyses and IHC evaluation.
Results: There were no differences in food consumption or body weight of mice between groups. Two mice experienced mild to moderate inflammation of the stomach. No other toxicities were observed. 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). IHC analysis revealed a reduction in the proliferative index, AR and NFκB expression, and an increase in apoptosis.
Conclusion: Further studies should be carried out to examine the efficacy for capsaicin as a radio-sensitizing agent in pre-clinical models.