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Analytical Determination of Mitochondrial Function of Excised Solid Tumor Homogenates
Published on: August 6, 2021
Amitriptyline down-regulates coenzyme Q10 biosynthesis in lung cancer cells
Tamara Ortiz1, Marina Villanueva-Paz2, Eduardo Díaz-Parrado3
1Dpto. 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.
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.
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