Acute oxidant damage promoted on cancer cells by amitriptyline in comparison with some common chemotherapeutic drugs
Acute oxidant damage promoted on cancer cells by amitriptyline in comparison with some common chemotherapeutic drugs
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DOI：
10.1097/cad.0b013e32833ed5f7
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发表时间：
2010-11-01
影响因子：
2.3
通讯作者：
de Miguel, Manuel
中科院分区：
文献类型：
--
作者：
David Cordero, Mario;Antonio Sanchez-Alcazar, Jose;de Miguel, Manuel
氧化治疗是一种相对较新的抗癌策略，其基于诱导高水平的氧化应激，通过增加细胞内活性氧（ROS）和/或通过耗尽肿瘤细胞的保护性抗氧化机制来实现。我们集中我们的调查阿米替林的抗肿瘤潜力在三个人类肿瘤细胞系：H460（肺癌），HeLa（宫颈癌），HepG 2（肝癌）;比较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，甲氨蝶呤。我们评估了肿瘤细胞的凋亡、ROS产生、线粒体质量和活性以及抗氧化防御。我们的研究结果表明，阿米替林产生最高的细胞损伤，诱导高水平的ROS，然后是不可逆的严重线粒体损伤。有趣的是，仅观察到阿米替林的抗氧化机制意外降低。总之，基于在肿瘤细胞中产生ROS和抑制抗氧化剂的能力，阿米替林成为一种有前途的抗癌治疗新药。Anti-Cancer Drugs 21：932-944（C）2010 Wolters Kluwer Health垂直栏Lippincott威廉姆斯& Wilkins.
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. Anti-Cancer Drugs 21:932-944 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.