Cytoprotective and anticancer properties of coenzyme Q versus capsaicin.
Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and serves as an electron donor and acceptor in mitochondrial energy-linked respiration. CoQ1 was shown to prevent ROS formation and cell death in complex 1 inhibited cells. Low concentrations of capsaicin like CoQ1 inhibited ROS formation but CoQ1 was more effective at restoring the mitochondrial membrane potential collapse caused by complex 1 inhibitors such as rotenone. At low concentrations, capsaicin acts as a CoQ mimic by protecting against rotenone induced ROS formation and mitochondrial membrane potential collapse. Lipid peroxidation in isolated rat hepatocytes induced by cumene hydroperoxide and chloroacetaldehyde was also prevented. At higher concentrations, capsaicin and CoQ1 became cytotoxic. Hep G2 cells were more susceptible than hepatocytes. The cytotoxic mechanism for both capsaicin and CoQ1 was shown to involve a collapse of the mitochondrial membrane potential, however, only capsaicin caused ROS formation. The capsaicin side chain was required for capsaicin induced cytotoxicity. The anticancer properties of CoQ1 and capsaicin should prove useful for inducing tumor cell apoptosis.
Galati
Giuseppe
G
Department of Pharmacology and Faculty of Pharmacy, University of Toronto, Toronto, Ont., Canada.
O'Brien
Peter J
PJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002211:Capsaicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008113:Liver Neoplasms / Q000473:pathology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014451:Ubiquinone / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D012402:Rotenone; D014451:Ubiquinone; C025203:Ubiquinone Q1; D002211:Capsaicin