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
