KMID : 1161420110140111344
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Journal of Medicinal Food 2011 Volume.14 No. 11 p.1344 ~ p.1351
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Suppression of Tumor Necrosis Factor-¥á-Induced Nuclear Factor ¥êB Activation and Aromatase Activity by Capsaicin and Its Analog Capsazepine
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Luqman Suaib
Meena Abha Marler Laura E. Kondratyuk Tamara P. Pezzuto John M.
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Abstract
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Target-specific drugs, including natural products, offer promise for the amelioration of cancer and other human ailments. Capsaicin, the pungent ingredient present in chilies (Capsicum annuum L.), and capsazepine, a synthetic analog of capsaicin (collectively referred to as vanilloids), are known to possess a variety of pharmacological and physiological properties. In our continuous effort to discover and characterize cancer chemopreventive agents from natural products, we investigated the effect of vanilloids on nuclear factor ¥ê-light-chain-enhancer of activated B cells (NF¥êB) activation using stably transfected 293/NF¥êB-Luc human embryonic kidney cells induced by treatment with tumor necrosis factor-¥á (TNF¥á) and on aromatase activity. Capsaicin and capsazepine blocked TNF¥á-induced NF¥êB activation in a dose-dependent manner with 50% inhibitory concentration (IC50) values of 0.68 and 4.2?¥ìM, respectively. No significant cytotoxicity was observed at the highest concentrations tested (53.1?¥ìM for capsazepine and 65.5?¥ìM for capsaicin). In addition, these vanilloids inhibited aromatase activity with IC50 values of 13.6 and 8.8?¥ìM, respectively. Computer-aided molecular docking studies showed docking scores indicative of good binding affinity of vanilloids with aromatase and NF¥êB. The highly conserved residues for capsaicin and capsazepine binding with NF¥êB p50 were Ser299 and Ile278 (H-bond 2.81A) and with NF¥êB p100 were Ser6, Arg82, Val86, Arg90 (H-bond 2.89A), Gly4, and Ser2 (H-bond 2.81A). The amino acids Trp224, Arg435, and Val373 (H-bond 2.80A) were found to be important for the binding of capsaicin and capsazepine with aromatase. Based on these findings, aromatase and NF¥êB are suggested as valid targets for these compounds; additional investigation of chemopreventive or chemotherapeutic potential is required.
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KEYWORD
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cancer chemoprevention, capsaicin, molecular docking, nociceptors, nuclear factor ¥ê-light-chain-enhancer of activated B cells, red pepper, tumor necrosis factor-¥á, vanilloids
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