Acute oxidant damage promoted on cancer cells by amitriptyline in comparison with some common chemotherapeutic drugs.
Oxidative therapy is a relatively new anticancer strategy based on the induction of high levels of oxidative stress, achieved by increasing intracellular reactive oxygen species (ROS) and/or by depleting the protective antioxidant machinery of tumor cells. We focused our investigations on the antitumoral potential of amitriptyline in three human tumor cell lines: H460 (lung cancer), HeLa (cervical cancer), and HepG2 (hepatoma); comparing the cytotoxic effect of amitriptyline with three commonly used chemotherapeutic drugs: camptothecin, doxorubicin, and methotrexate. We evaluated apoptosis, ROS production, mitochondrial mass and activity, and antioxidant defenses of tumor cells. Our results show that amitriptyline produces the highest cellular damage, inducing high levels of ROS followed by irreversible serious mitochondrial damage. Interestingly, an unexpected decrease in antioxidant machinery was observed only for amitriptyline. In conclusion, based on the capacity of generating ROS and inhibiting antioxidants in tumor cells, amitriptyline emerges as a promising new drug to be tested for anticancer therapy.
Cordero
Mario David
MD
Departamento Citología e Histología Normal y Patológica, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain.
Sánchez-Alcázar
José Antonio
JA
Bautista-Ferrufino
María Rosa
MR
Carmona-López
María Inés
MI
Illanes
Matilde
M
Ríos
María José
MJ
Garrido-Maraver
Juan
J
Alcudia
Ana
A
Navas
Plácido
P
de Miguel
Manuel
M
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003603:Cytotoxins / Q000494:pharmacology; D058492:Drug Repositioning; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009928:Organ Specificity; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000032:analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
D000970:Antineoplastic Agents; D003603:Cytotoxins; D016877:Oxidants; D017382:Reactive Oxygen Species; D000639:Amitriptyline