title: Vanilloid receptor agonists and antagonists are mitochondrial inhibitors: how vanilloids cause non-vanilloid receptor mediated cell death.
abstract: Time-lapse photomicroscopy of human H460 lung cancer cells demonstrated of the transient receptor potential V1 (TRPV1) channel agonists, (E)-capsaicin and resiniferatoxin, and the TRPV1 antagonists, capsazepine, and SB366791, were able to bring about morphological changes characteristic of apoptosis and/or necrosis. Immunoblot analysis identified immunoreactivity for the transient receptor potential V1 (TRPV1) channel in rat brain samples, but not in rat heart mitochondria or in H460 cells. In isolated rat heart mitochondria, all four ligands caused concentration-dependent decreases in oxygen consumption and mitochondrial membrane potential. (E)-Capsaicin and capsazepine evoked concentration-dependent increases and decreases, respectively, in mitochondrial hydrogen peroxide production, whilst resiniferatoxin and SB366791 were without significant effect. These data support the hypothesis that (E)-capsaicin, resiniferatoxin, capsazepine, and SB366791 are all mitochondrial inhibitors, able to activate apoptosis and/or necrosis via non-receptor mediated mechanisms, and also support the use of TRPV1 ligands as anti-cancer agents.
authors.affiliation: School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, UK.
authors.forename: Andriani
authors.initials: A
authors.lastname: Athanasiou
authors.forename: Paul A
authors.initials: PA
authors.lastname: Smith
authors.forename: Sara
authors.initials: S
authors.lastname: Vakilpour
authors.forename: Nethia M
authors.initials: NM
authors.lastname: Kumaran
authors.forename: Amy E
authors.initials: AE
authors.lastname: Turner
authors.forename: Dimitra
authors.initials: D
authors.lastname: Bagiokou
authors.forename: Robert
authors.initials: R
authors.lastname: Layfield
authors.forename: David E
authors.initials: DE
authors.lastname: Ray
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Westwell
authors.forename: Stephen P H
authors.initials: SP
authors.lastname: Alexander
authors.forename: David A
authors.initials: DA
authors.lastname: Kendall
authors.forename: Dileep N
authors.initials: DN
authors.lastname: Lobo
authors.forename: Susan A
authors.initials: SA
authors.lastname: Watson
authors.forename: Artitaya
authors.initials: A
authors.lastname: Lophatanon
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Muir
authors.forename: De-An
authors.initials: DA
authors.lastname: Guo
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Bates
mesh_terms: D000813:Anilides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002934:Cinnamates / Q000008:administration & dosage / Q000494:pharmacology*; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism
chemical_list: D000813:Anilides; D002934:Cinnamates; D004224:Diterpenes; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C024353:resiniferatoxin; D006861:Hydrogen Peroxide; C071423:capsazepine; D002211:Capsaicin