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Acute oxidant damage promoted on cancer cells by amitriptyline in comparison with some common chemotherapeutic drugs

AuthorsCordero, Mario D. ; Sánchez-Alcázar, José Antonio ; Garrido-Maraver, Juan; Navas, Plácido ; Miguel, Manuel de
Chemotherapeutic drugs
Mitochondial damage
Oxidative stress
Oxidation therapy
Reactive oxygen species
Issue DateOct-2010
PublisherLippincott Williams & Wilkins
CitationAnti Cancer Drugs 21(10): 932-944 (2010)
AbstractOxidative 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.
Description13 páginas, 8 figuras.-- et al.
Publisher version (URL)http://dx.doi.org/10.1097/CAD.0b013e32833ed5f7
Appears in Collections:(CABD) Artículos
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