Capsaicin: a novel radio-sensitizing agent for prostate cancer

Abstract

Introduction: Radio-sensitizing agents sensitize tumor cells to the lethal effects of radiotherapy (RT) allowing for use of lower doses of radiation to achieve equivalent cancer control, while minimizing adverse effects to normal tissues. Given their limited toxicity and ability to easily integrate into the diet, compounds occurring naturally in the diet make ideal potential radio-sensitizing agents. In this study, we have examined whether capsaicin, the active compound in chilli peppers, can modulate the response to RT in preclinical models of prostate cancer (PCa).

Methods: The effects of RT (1-8 Gy) and/or capsaicin (1-10 µM) on colony formation rates in human PCa cells were assessed using clonogenic assays. Mechanistic studies were performed by Western Blot, immunocytochemistry, and flow cytometry. Athymic mice (n = 40) were inoculated with human LNCaP cells. Once tumors reached 100 mm(3) , animals were randomized into four groups: control, capsaicin alone (5 mg/kg/d), RT alone (6 Gy), and capsaicin and RT.

Results: Capsaicin reduced colony formation rates and radio-sensitized human PCa cells (Sensitizer enhancement ratio = 1.3) which corresponded to the suppression of NFκB, independent of TRP-V1 receptor. Cell cycle modulation occurred following RT and capsaicin treatment independently. In vivo, oral administration of capsaicin with RT resulted in a 'greater than additive' growth delay and reduction in the tumor growth rate greater than capsaicin (P < 0.001) or RT (P < 0.03) alone. Immunohistochemical analysis revealed a reduction in proliferation and NFκB expression, and increase in DNA damage.

Discussion: Our findings suggest that capsaicin acts as a radio-sensitzing agent for PCa through the inhibition of NFκB signalling.

Keywords: NFκB signalling; capsaicin; natural compound; prostate neoplasm; radiation; radiosenisitizing agent; therapeutic ratio.