Redox imbalance and biochemical changes in cancer.
Redox imbalance and biochemical changes in cancer.
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DOI：
10.1158/0008-5472.can-13-1117
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发表时间：
2013-10-15
期刊：
影响因子：
11.2
通讯作者：
Oberley TD
中科院分区：
文献类型：
--
作者：
Jorgenson TC;Zhong W;Oberley TD
对于这篇观点文章，我们探索一个假设，涉及还原/氧化(氧化)状态在癌症中可能发挥的作用。我们推测，在癌症进展过程中观察到的细胞大分子的许多修饰可能是由氧化还原失衡引起的。最近的生化数据表明，与良性的原代前列腺上皮细胞相比，人类前列腺癌细胞株表现出氧化还原不平衡(氧化)；氧化的程度因每种细胞系的侵袭行为而异。我们最近的数据表明，与良性邻近的乳腺组织相比，人类乳腺癌组织表现出氧化还原失衡(减少)。本文总结的越来越多的数据表明，氧化还原失衡可能通过翻译后修饰调节基因表达和改变蛋白质稳定性，进而调节现有的细胞程序。尽管癌症治疗方法有了很大的改进，但还是会出现耐药性，氧化还原失衡可能在这一过程中发挥了作用。研究表明，一些癌症治疗药物会增加活性氧/氮物种和抗氧化酶的生成，这可能会改变总的抗氧化能力，导致细胞适应，并导致治疗方式的有效性降低。涉及调节细胞内和细胞外氧化还原状态的方法结合其他治疗方法可能会带来新的治疗选择，特别是对标准治疗耐药的患者。
For this Perspectives article, we explore a hypothesis involving the possible role of reduction/oxidation (redox) state in cancer. We hypothesize many modifications in cellular macromolecules observed in cancer progression may be caused by redox imbalance. Recent biochemical data suggest human prostate cancer cell lines demonstrate a redox imbalance (oxidizing) compared to benign primary prostate epithelial cells; the degree of oxidation varied with aggressive behavior of each cell line. Our recent data suggest human breast cancer tissues demonstrate a redox imbalance (reducing) compared to benign adjacent breast tissues. Accumulating data summarized in this article suggest redox imbalance may regulate gene expression and alter protein stability by posttranslational modifications, in turn modulating existing cellular programs. Despite significant improvements in cancer therapeutics, resistance occurs, and redox imbalance may play a role in this process. Studies demonstrate some cancer therapeutic agents increase generation of reactive oxygen/nitrogen species and antioxidant enzymes, which may alter total antioxidant capacity, cause cellular adaptation, and result in reduced effectiveness of treatment modalities. Approaches involving modulations of intra- and extracellular redox states in combination with other therapies may lead to new treatment options, especially for patients resistant to standard treatments.