Departamento Citología e Histología Normal y Patológica, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain.
Anticancer Drugs. 2010 Nov;21(10):932-44. doi: 10.1097/CAD.0b013e32833ed5f7.
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.
氧化疗法是一种相对较新的抗癌策略，基于诱导高水平的氧化应激，通过增加细胞内的活性氧物种（ROS）和/或耗尽肿瘤细胞的保护性抗氧化机制来实现。我们将研究重点放在阿米替林在三种人类肿瘤细胞系中的抗肿瘤潜力上：H460（肺癌）、HeLa（宫颈癌）和 HepG2（肝癌）；将阿米替林的细胞毒性作用与三种常用的化疗药物：喜树碱、阿霉素和甲氨蝶呤进行比较。我们评估了肿瘤细胞的细胞凋亡、ROS 产生、线粒体质量和活性以及抗氧化防御。我们的结果表明，阿米替林产生的细胞损伤最大，诱导高水平的 ROS，随后导致不可逆的严重线粒体损伤。有趣的是，只有阿米替林观察到抗氧化机制的意外下降。总之，基于在肿瘤细胞中产生 ROS 和抑制抗氧化剂的能力，阿米替林作为一种有前途的新药物，有望用于癌症治疗的测试。
