Synergistic effect of VR1 agonist Capsaicin and its antagonist IRTX, in tumor cell apoptosis: implication for involvement of VR1 (49.24)

Abstract

Abstract Capsaicin (CP) is the principal pungent ingredient of red peppers. The CP receptor, VR1 has been shown to be highly expressed by nociceptive neurons in dorsal root and trigeminal ganglia. Recently we have demonstrated that intratumoral administration of CP into a preexisting tumor results in retarded progression of the injected tumor. Here we report that tumor cells express VR1 and treatment with CP leads to tumor cell death by apoptosis as evidenced by positive TUNEL staining. Unlike tumor cells normal embryonic fibroblasts (MEFS) do not succumb to apoptosis by this treatment. CP treatment induced up-regulation of reactive oxygen species (ROS) and Caspase-3 activation in a dose-dependent manner. Further, we observed that VR1 antagonist I-RTX has synergistic apoptotic effect with CP like a partial agonist of VR1, indicating the involvement of VR1 in this apoptotic event. We also report that CP treatment leads to degradation of FAF1 (Fas associated factor1) a VR1 associated protein in a dose-dependent manner. In summary, our data suggests that VR1 engagement and subsequent degradation of FAF1 is one of the mechanisms of CP mediated apoptosis in tumor cells.