Mechanisms of vanilloid-induced apoptosis

Chemical compounds that contain the vanillyl moiety (4-hydroxy-3-methoxybenzyl) are collectively classified as vanilloids. Vanilloid phytochemicals can be found in a variety of sources, some of which are routinely consumed by humans throughout the world. The dietary and/or medicinal use of vanilloids may be effective in inhibiting or reversing carcinogenesis, which has sparked a considerable interest in these compounds as potential chemopreventive or chemotherapeutic agents. Certain vanilloids are also valuable as pharmacological tools for investigating neurobiology, and have been proven effective in alleviating neurogenic pain and inflammation. Recently several vanilloids have demonstrated the ability to induce apoptosis in various cell types. Vanilloids can interact with proteins and membranes to initiate pleiotropic effects, some of which are potentially cytotoxic. Certain vanilloids bind to cation channels on nociceptive sensory neurons to regulate Ca²⁺ uptake, which can promote neurotoxicity resulting in apoptosis and necrosis. Furthermore, some vanilloids appear to interfere with enzymatic processes in the plasma membrane and the mitochondria by functioning as coenzyme Q antagonist. This can promote reactive oxygen species production and/or the disruption of redox homeostasis resulting in apoptosis. This review will examine the cellular targets, cytotoxic effects, and the downstream effector mechanisms associated with vanilloid-induced apoptosis.