The thioredoxin system: a key target in tumour and endothelial cells
The thioredoxin system: a key target in tumour and endothelial cells
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DOI：
10.1259/bjr/34180435
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发表时间：
2008-01-01
影响因子：
2.6
通讯作者：
Martin, S. G.
中科院分区：
文献类型：
--
作者：
Mukherjee, A.;Martin, S. G.
硫氧还蛋白是一种氧化还原敏感性分子，具有多效性细胞效应，例如控制增殖、氧化还原状态和凋亡，并且通常在恶性肿瘤中上调。该系统通过巯基转移控制许多转录因子的激活，并且通过其对缺氧诱导因子Ia的活性，它能够调节血管内皮生长因子水平，从而调节血管生成。已显示硫氧还蛋白蛋白在某些肿瘤的缺氧区域中上调，表明抑制剂可能潜在地表现出增强的缺氧毒性和/或间接抗血管生成作用。这方面的证据在文献中越来越明显。目前的报告审查硫氧还蛋白系统作为抗癌药物的目标，并集中在两个最近的化合物，PMX 464和PX 12，据报道，抑制这一重要途径。
Thioredoxin is a redox-sensitive molecule that has pleiotropic cellular effects, such as the control of proliferation, redox states and apoptosis, and is often upregulated in malignancy. The system controls the activation of a number of transcription factors through sulphydryl transfer and, through its activity on hypoxia inducible factor la, it is able to regulate vascular endothelial growth factor levels and hence angiogenesis. The thioredoxin protein has been shown to be upregulated in hypoxic regions of certain tumours, suggesting that inhibitors could potentially exhibit enhanced hypoxic toxicity and/or indirect anti-angiogenic effects. Evidence of this is becoming apparent in the literature. The current report reviews the thioredoxin system as an anticancer drug target and focuses upon two recent compounds, PMX464 and PX12, which reportedly inhibit this important pathway.