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Utilization of redox modulating small molecules that selectively act as pro-oxidants in cancer cells to open a therapeutic window for improving cancer therapy
Redox Biology ( IF 11.4 ) Pub Date : 2021-01-16 , DOI: 10.1016/j.redox.2021.101864
M S Petronek 1 , J M Stolwijk 1 , S D Murray 2 , E J Steinbach 1 , Y Zakharia 3 , G R Buettner 1 , D R Spitz 1 , B G Allen 1
Affiliation  

There is a rapidly growing body of literature supporting the notion that differential oxidative metabolism in cancer versus normal cells represents a metabolic frailty that can be exploited to open a therapeutic window into cancer therapy. These cancer cell-specific metabolic frailties may be amenable to manipulation with non-toxic small molecule redox active compounds traditionally thought to be antioxidants. In this review we describe the potential mechanisms and clinical applicability in cancer therapy of four small molecule redox active agents: melatonin, vitamin E, selenium, and vitamin C. Each has shown the potential to have pro-oxidant effects in cancer cells while retaining antioxidant activity in normal cells. This dichotomy can be exploited to improve responses to radiation and chemotherapy by opening a therapeutic window based on a testable biochemical rationale amenable to confirmation with biomarker studies during clinical trials. Thus, the unique pro-oxidant/antioxidant properties of melatonin, vitamin E, selenium, and vitamin C have the potential to act as effective adjuvants to traditional cancer therapies, thereby improving cancer patient outcomes.



中文翻译:

利用氧化还原调节小分子选择性地充当癌细胞中的促氧化剂,为改善癌症治疗打开治疗窗口

越来越多的文献支持这样一种观点,即癌症正常细胞中氧化代谢的差异代表了一种代谢脆弱性,可以利用这种脆弱性来打开癌症治疗的治疗窗口。这些癌细胞特异性的代谢弱点可能适合用传统上被认为是抗氧化剂的无毒小分子氧化还原活性化合物来操纵。在这篇综述中,我们描述了四种小分子氧化还原活性剂在癌症治疗中的潜在机制和临床适用性:褪黑激素、维生素 E、硒和维生素 C。每种药物都显示出在癌细胞中具有促氧化作用的潜力,同时保留抗氧化剂正常细胞中的活性。这种二分法可以用来改善对放疗和化疗的反应,通过打开一个基于可测试的生化原理的治疗窗口,该原理可以在临床试验期间通过生物标志物研究进行确认。因此,褪黑激素、维生素 E、硒和维生素 C 独特的促氧化/抗氧化特性有可能成为传统癌症治疗的有效佐剂,从而改善癌症患者的治疗效果。

更新日期:2021-01-18
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