Amitriptyline down-regulates coenzyme Q10 biosynthesis in lung cancer cells

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 Q (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.This work has been supported by the Spanish research association FOICAM (Asociación para el Fomento de la Investigación en Cáncer y Mitocondriopatías), FIS PI10/00543 grant, Fondo Europeo de Desarrollo Regional (FEDER-Unión Europea), SAS 111242 grant (Servicio Andaluz de Salud-Junta de Andalucía), and Proyecto de Investigación de Excelencia (Junta de Andalucía CTS-5725).Peer Reviewe