Affiliations: Department of Pharmacology and Faculty of Pharmacy,
University of Toronto, Toronto, Ont., Canada
Note: [] Address for correspondence: Faculty of Pharmacy, University of
Toronto, 19 Russell St., Rm 522, Toronto, Ont., Canada, M5S 2S2. Tel.: +1 416
978 2716; Fax: +1 416 978 8511; E-mail: peter.obrien@utoronto.ca
Abstract: 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. CoQ_{1} was shown
to prevent ROS formation and cell death in complex 1 inhibited cells. Low
concentrations of capsaicin like CoQ_{1} inhibited ROS
formation but CoQ_{1} 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 CoQ_{1} became cytotoxic. Hep
G2 cells were more susceptible than hepatocytes. The cytotoxic mechanism for
both capsaicin and CoQ_{1} 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 CoQ_{1} and
capsaicin should prove useful for inducing tumor cell apoptosis.
Keywords: coenzyme Q, capsaicin, hepatocytes, Hep G2 cells, mitochondria, anticancer
Journal: BioFactors, vol. 18, no. 1-4, pp. 195-205, 2003
