Capsaicin (CAP), a highly selective agonist for transient receptor potential vanilloid type 1 (TRPV1), has been widely reported to exhibit anti-oxidant, anti-inflammation and anticancer activities. Currently, several therapeutic approaches for bladder cancer (BCa) are available, but accompanied by unfavorable outcomes. Previous studies reported a potential clinical effect of CAP to prevent BCa tumorigenesis. However, its underlying molecular mechanism still remains unknown. Our transcriptome analysis suggested a close link among calcium signaling pathway, cell cycle regulation, ROS metabolism and FOXO signaling pathway in BCa. In this study, several experiments were performed to investigate the effects of CAP on BCa cells (5637 and T24) and NOD/SCID mice. Our results showed that CAP could suppress BCa tumorigenesis by inhibiting its proliferation both in vitro and in vivo. Moreover, CAP induced cell cycle arrest at G0/G1 phase and ROS production. Importantly, our studies revealed a strong increase of FOXO3a after treatment with CAP. Furthermore, we observed no significant alteration of apoptosis by CAP, whereas Catalase and SOD2 were considerably upregulated, which could clear ROS and protect against cell death. Thus, our results suggested that CAP could inhibit viability and tumorigenesis of BCa possibly via FOXO3a-mediated pathways.
Keywords: ROS; bladder cancer; capsaicin; cell cycle; migration; xenograft.