Capsaicin enhances chemosensitivity and mitigates MMP11-driven aggressiveness in human bladder cancer

Abstract Bladder cancer (BLCA) is the second most common malignant cancer of the male urological system. BLCA is characterized by a high rate of recurrence. Capsaicin is increasingly being used in cancer treatment. This study analyzed the inhibitory effects of capsaicin on cell invasiveness and examined whether capsaicin enhances the chemosensitivity of BLCA. High concentrations of capsaicin induced apoptosis in cancer cells. Co-administration of capsaicin with various chemotherapy drugs (cisplatin, epirubicin, and mitomycin C) increased cancer cell sensitivity to chemotherapy. At lower concentrations, capsaicin effectively inhibited cell invasiveness by downregulating MMP11 expression. Mechanistically, capsaicin suppressed MMP11 expression through the transient receptor potential vanilloid 1 receptor and the p38/extracellular signal-regulated kinase/c-Jun signaling pathway. Functional analysis revealed a positive correlation between the expression level of MMP11 and various ontogenetic properties of BLCA. MMP11 expression was positively correlated with clinical staging, muscle-invasive bladder cancer, lymphatic metastasis, and poor prognosis in patients with BLCA. These findings suggest that MMP11 has potential as a clinical prognostic marker for BLCA. Finally, capsaicin demonstrated significant tumor growth suppression and enhanced chemosensitivity in vivo. Taken together, capsaicin may promote apoptosis, inhibit cell invasion in vitro, and suppress tumor growth in vivo. Combining capsaicin with first-line chemotherapeutic drugs may enhance their efficacy against BLCA, and therefore, which indicates that capsaicin has promise as a clinical medication.