Antioxidant inhibitors for cancer therapy
Antioxidant inhibitors for cancer therapy
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DOI：
10.1016/s0306-9877(98)90036-6
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发表时间：
1998-11-01
影响因子：
4.7
通讯作者：
Lillehei, KO
中科院分区：
文献类型：
--
作者：
Kong, Q;Lillehei, KO
内置的细胞防御机制在肿瘤抵抗非手术抗肿瘤治疗中发挥着重要作用。其中，超氧化物歧化酶（SOD）等抗氧化剂的过度表达可能是最重要的。氧自由基具有剧毒，与多种疾病有关，包括致癌和衰老。它们通过脂质过氧化和DNA损伤产生多种病理变化。因此，用抗氧化剂治疗自由基引起的疾病已成为公认的治疗方法。然而，讽刺的是，大多数化疗药物和电离辐射杀死肿瘤细胞的根本机制并不是增加抗氧化作用，而是产生更多自由基，导致不可逆的组织损伤。非手术抗肿瘤治疗后活性氧 (ROS) 的小幅增加会诱导 SOD 等抗氧化剂的表达，但相反，ROS 的过量产生会耗尽 SOD 和其他适应性抗氧化防御的产生。基于这些考虑，我们假设适当施用抗氧化剂抑制剂和/或自由基生成化合物可能是治疗实体瘤的有用策略。
Built-in cellular defense mechanisms play a major role in a tumor's protection against non-surgical antineoplastic therapies. Of these, the overexpression of antioxidants such as superoxide dismutase (SOD) may be the most important. Oxygen radicals are highly toxic, and have been implicated in various diseases, including carcinogenesis and aging. They produce a variety of pathological changes through lipid peroxidation and DNA damage. Therefore, treating free-radical-induced diseases with antioxidants has been an accepted therapeutic approach. Ironically, however, the underlying mechanism that most chemotherapeutic agents and ionizing radiation exert on tumor cell kill is not increased antioxidation but rather the production of more free radicals leading to irreversible tissue injury. A small increase in reactive oxygen species (ROS) following non-surgical antineoplastic therapies induces the expression of antioxidants such as SOD, but overproduction of ROS, conversely, exhausts the production of SOD and other adaptive antioxidant defenses. Based on these considerations, we hypothesize that the appropriate administration of antioxidant inhibitors and/or free-radical-generating compounds may be a useful strategy in the treatment of solid tumors.