摘要
与正常细胞相比,肿瘤细胞显示了较高的活性氧簇水平,并且氧化还原环境发生改变。过高的活性氧水平对这些细胞是有毒性的,因此他们变得更加容易被药物诱导进一步产生的活性氧侵袭。然而,抗氧化能力的上调在适应癌细胞内在氧化应激时可以赋予其耐药性。因此, 通过氧化还原调节,消除这样的耐药机制有显著的治疗意义。许多氧化还原调节剂已经开发出来。氧化还原激活系统体现在抗坏血酸醌氧化还原循环和氧化还原抑制剂维生素E琥珀酸类似物(如α-生育酚琥珀酸盐)已被证明可选择性诱导不同类型的癌症细胞死亡。通过破坏细胞器如线粒体,释放细胞凋亡因子的潜力体现了这些化合物的协同作用,导致有效的恶性细胞的死亡和肿瘤生长的抑制。与这个观点一致,临床试验旨在研究新型氧化还原调节剂的治疗效果。
关键词: 细胞凋亡,自我吞噬,氧化还原活性剂,氧化还原抑制剂,基于ROS的癌症治疗,维他命E类似物
Current Medicinal Chemistry
Title:Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer
Volume: 22 Issue: 5
Author(s): M. Tomasetti, L. Santarelli, R. Alleva, Lan-Feng Dong and J. Neuzil
Affiliation:
关键词: 细胞凋亡,自我吞噬,氧化还原活性剂,氧化还原抑制剂,基于ROS的癌症治疗,维他命E类似物
摘要: Tumours exhibit higher basal levels of reactive oxygen species (ROS) and altered redox environment compared to normal cells. Excessive level of ROS can be toxic to these cells, thus they become more vulnerable to damage by further ROS insults induced by pharmacological agents. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Therefore, abrogation of such drugresistant mechanisms by redox modulation could have significant therapeutic implications. Many redox-modulating agents have been developed. The redox-active system epitomised by ascorbate-driven quinone redox cycling, and the group of redox-silent vitamin E analogues represented by α-tocopheryl succinate have been shown to induce selective cancer cell death in different types of cancer. These compounds synergistically act by destabilising organelles like mitochondria, unleashing their apoptogenic potential, which results in efficient death of malignant cells and suppression of tumour growth. Consistent with this notion, clinical trials that aim to examine the therapeutic performance of novel redoxmodulating drugs in cancer patients are currently under way.
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Cite this article as:
M. Tomasetti, L. Santarelli, R. Alleva, Lan-Feng Dong and J. Neuzil , Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer, Current Medicinal Chemistry 2015; 22 (5) . https://dx.doi.org/10.2174/0929867321666140915142219
DOI https://dx.doi.org/10.2174/0929867321666140915142219 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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