Capsaicin as a Novel Chemopreventive and Therapeutic Option for Prostate Cancer

Capsaicin, the active compound in chilli peppers, has been reported to have anti-carcinogenic properties. In the following thesis, the chemopreventive and therapeutic potential of capsaicin on prostate cancer has been investigated.;To examine the chemopreventive properties of capsaicin, in vitro studies were carried out using a panel of prostate cancer cell lines. Here, it was deduced that capsaicin alone and in combination with the antioxidant lycopene significantly reduced the proliferation and induced apoptosis in a dose-dependent manner. Detailed mechanistic studies revealed that these effects were predominately mediated though intrinsic apoptosis. Based on these studies, the effect of capsaicin was assessed using a transgenic chemoprevention model of prostate cancer. Long-term oral administration of capsaicin reduced the tumour grade and metastatic burden in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, compared to control mice.;To understand the therapeutic value of capsaicin, prostate cancer radio-sensitivity studies were carried out using various pre-clinical models. A dose-dependent growth inhibition in colony survival was demonstrated in prostate cancer cell lines following exposure to capsaicin with radiotherapy. Using the LNCaP xenograft mouse model, capsaicin and radiation therapy reduced the growth of prostate cancer tumours over time, greater than either monotherapy. A number of mechanisms were involved in mediating these effects, including the suppression of the NFkappaB pathway. Interestingly, the TRP-V1 capsaicin receptors were present on prostate cancer cells; however, they were not found to predominately mediate the anti-cancer effects of capsaicin.;Evidence from this thesis has formed the basis for a clinical trial that is currently examining the effect of capsaicin supplementation on prostate cancer patients. If this trial proves to show benefit of capsaicin supplementation on prostate cancer, it may be integrated into the management and treatment strategies for prostate cancer, thus reducing the morbidity and mortality of the disease.