Inhibiton of NFκB activation and aromatase activity by vanilloids: An in vitro and in silico study

Abstract

Target-specific drugs, including natural products, offer promise for the amelioration of cancer and other human ailments with reduced side-effects. Capsaicin, the pungent ingredient present in chillies (Capsicum annuum L.), and capsazepine, a synthetic analogue of capsaicin (collectively referred to as vanilloids), are known to possess a variety of pharmacological and physiological properties. In our continuous effort to discover cancer chemopreventive agents from natural products, we investigated the effect of vanilloids on NFκB activation with stably transfected 293/NFκB-Luc human embryonic kidney cells induced by treatment with tumor necrosis factor (TNFα), and aromatase activity. Capsaicin and capsazepine blocked TNFα-induced NFκB activation in a dose-dependent manner with IC50 values of 13.5 and 8.5 μM, respectively. No cytotoxicity was observed at higher test concentration (20 μg/mL). In addition, these vanilloids inhibited aromatase activity with IC50 values of 0.68 and 4.21 μM, respectively. Computer aided molecular docking studies showed acceptable docking scores indicating good binding affinity of vanilloids with aromatase and NFκB. Based on these findings, aromatase and NFκB are suggested as valid targets for these compounds; additional investigation of chemopreventive or chemotherapeutic potential is required.