title: Amitriptyline down-regulates coenzyme Q10biosynthesis in lung cancer cells.
abstract: Amitriptyline, a tricyclic antidepressant, has been proposed as an antitumoral drug in oxidative therapy. Its pro-apoptotic effects, mediated by high reactive oxygen species generation, have been already described. In this study we analysed the effect of amitriptyline on the biosynthesis of coenzyme Q10(CoQ), an essential component for electron transport and a potent membrane antioxidant involved in redox signaling. We treated H460 cells, a non-small-cell lung cancer cell line, with amitriptyline and we analysed CoQ levels by HPLC and CoQ biosynthesis rate, as well as the enzymes involved in CoQ biosynthesis by real-time PCR and Western blot. Amitriptyline treatment induced a dose-dependent decrease in CoQ levels in tumor cells. CoQ decreased levels were associated with down-regulation of the expression of COQ4 gene, as well as decreased Coq4 and Coq6 protein levels. Our findings suggest that the effect of amitriptyline on CoQ biosynthesis highlights the potential of this drug for antitumoral oxidative therapy.
authors.affiliation: Dpto. Citología e Histología Normal y Patológica, Facultad de Medicina, Universidad de Sevilla, Avda. Sánchez Pizjuán s/n, 41009 Sevilla, Spain; Escuela de Nutrición y Dietética, Facultad de Ciencias de la Salud, Universidad del Desarrollo, Concepción, Chile.
authors.forename: Tamara
authors.initials: T
authors.lastname: Ortiz
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Carretera de Utrera, 41013 Sevilla, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Villanueva-Paz
authors.affiliation: Dpto. Citología e Histología Normal y Patológica, Facultad de Medicina, Universidad de Sevilla, Avda. Sánchez Pizjuán s/n, 41009 Sevilla, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Díaz-Parrado
authors.affiliation: Dpto. Citología e Histología Normal y Patológica, Facultad de Medicina, Universidad de Sevilla, Avda. Sánchez Pizjuán s/n, 41009 Sevilla, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Illanes
authors.affiliation: Dpto. Citología e Histología Normal y Patológica, Facultad de Medicina, Universidad de Sevilla, Avda. Sánchez Pizjuán s/n, 41009 Sevilla, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández-Rodríguez
authors.affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Carretera de Utrera, 41013 Sevilla, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Sánchez-Alcázar
authors.affiliation: Dpto. Citología e Histología Normal y Patológica, Facultad de Medicina, Universidad de Sevilla, Avda. Sánchez Pizjuán s/n, 41009 Sevilla, Spain. Electronic address: mmiguel@us.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: de Miguel
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D014451:Ubiquinone; D000639:Amitriptyline; C024989:coenzyme Q10
keywords: Amitriptyline; Antioxidants; Coenzyme Q(10); Oxidative stress; Oxidative therapy