Lycopene enhances the anti-proliferative and pro-apoptotic effects of capsaicin in prostate cancer in vitro

Background: Increasing evidence suggests dietary factors influence the development and progression of prostate cancer (PCa). The chemopreventive properties of lycopene, the antioxidant found in tomatoes, have been extensively studied for PCa; however, the effect of lycopene, as a single agent, remains unclear. Studies that are more promising, involve using lycopene in combination with other dietary agents. Capsaicin, the active compound in chilli peppers, is reported to exert potent anti-cancer effects in both in vitro and in vivo PCa models. We have investigated whether lycopene enhances the anti-proliferative and apoptotic effects of capsaicin in vitro. Methods: Using the MTS Cell Proliferation Assay we assessed the anti-proliferative effect of capsaicin alone, or in combination with lycopene in human PCa cell lines (LNCaP, PC3, PC3-AR2, DU145) and prostate stromal cells. Flow cytometry and Western Blotting techniques were used to assess potential mechanisms of interaction. Results: Capsaicin exhibited anti-proliferative and pro-apoptotic effects, which were significantly enhanced with the addition of lycopene to PCa cells. The greatest effects were observed in androgen-sensitive cell lines. Detailed mechanistic studies revealed this combination may be interrupting the androgen-signaling pathways; independent of TRP-V1 signaling. Cell cycle analysis revealed that capsaicin and lycopene induce a cell cycle arrest, corresponding to alterations in tumor-suppressor proteins. Treating LNCaP cells with capsaicin and lycopene also altered proteins involved the apoptosis signaling pathway including, cleaved PARP, Caspase-3 and Bax/Bcl-xL expression. Conclusions: Our results suggest that lycopene enhances the anti-cancer properties of capsaicin. Understanding micronutrient interactions may help improve current chemoprevention strategies.