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Amitriptyline down-regulates coenzyme Q10 biosynthesis in lung cancer cells

AutorOrtiz, Tamara; Villanueva Paz, Marina; Díaz-Parrado, Eduardo; Illanes, Matilde; Fernández-Rodríguez, Ana; Sánchez-Alcázar, José Antonio ; Miguel, Manuel de
Palabras claveCoenzyme Q10
Amitriptyline
Oxidative stress
Antioxidants
Oxidative therapy
Fecha de publicación2017
EditorElsevier
CitaciónEuropean Journal of Pharmacology 797: 75-82 (2017)
ResumenAmitriptyline, 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.
URIhttp://hdl.handle.net/10261/163448
Identificadoresdoi: 10.1016/j.ejphar.2017.01.017
e-issn: 1879-0712
issn: 0014-2999
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