Glucose deprivation-induced metabolic oxidative stress and cancer therapy.
Glucose deprivation-induced metabolic oxidative stress and cancer therapy.
复制标题
DOI：
10.4103/0973-1482.55133
复制
发表时间：
2009-09
影响因子：
1.3
通讯作者：
Spitz DR
中科院分区：
文献类型：
--
作者：
Simons AL;Mattson DM;Dornfeld K;Spitz DR
癌细胞(与正常细胞相比)表现出氧化应激、糖酵解增加和戊糖循环活性增加的证据。癌细胞中的氧化应激被认为是由于线粒体功能障碍导致过氧化氢水平增加而引起的，癌细胞被提出通过增加葡萄糖代谢来弥补这一缺陷。葡萄糖代谢也被证明通过形成丙酮酸(来自糖酵解)和NADPH(来自戊糖循环)在氢过氧化氢解毒中发挥作用。此外，在癌细胞中，葡萄糖缺乏以及2-脱氧葡萄糖(2-DG)的治疗已被证明会导致氧化应激和细胞毒性。此外，转化细胞比未转化细胞更容易受到葡萄糖剥夺(和2DG-)诱导的细胞毒性和氧化应激的影响。这些结果支持这一假说，即癌细胞线粒体呼吸缺陷导致O2·-和H_2O_2稳态水平增加，葡萄糖代谢增加以弥补这一缺陷。讨论了这些发现在开发使用2DG和氢过氧化氢代谢抑制剂来诱导放射/化学增敏的癌症治疗中的应用，以及FDG-PET成像可以预测肿瘤对这些治疗的反应的可能性。
Cancer cells (vs. normal cells) demonstrate evidence of oxidative stress, increased glycolysis, and increased pentose cycle activity. The oxidative stress in cancer cells has been hypothesized to arise from mitochondrial dysfunction leading to increased levels of hydroperoxides, and cancer cells have been proposed to compensate for this defect by increasing glucose metabolism. Glucose metabolism has also been shown to play a role in hydroperoxide detoxification via the formation of pyruvate (from glycolysis) and NADPH (from the pentose cycle). Furthermore, in cancer cells, glucose deprivation as well as treatment with 2-deoxyglucose (2 DG) has been shown to induce oxidative stress and cytotoxicity. Additionally, transformed cells have been shown to be more susceptible to glucose deprivation (and 2DG-)-induced cytotoxicity and oxidative stress than untransformed cells. These results support the hypothesis that cancer cells have a defect in mitochondrial respiration leading to increased steady state levels of O2•- and H2O2, and glucose metabolism is increased to compensate for this defect. The application of these findings to developing cancer therapies using 2DG combined with inhibitors of hydroperoxide metabolism to induce radio/chemosensitization is discussed, as well as the possibility that FDG-PET imaging may predict tumor responses to these therapies.
登录
查看更多内容
影响因子：
8.8
作者：
Halfpenny, W;Hain, S F;Biassoni, L;Maisey, M N;Sherman, J A;McGurk, M
通讯作者：
McGurk, M
影响因子：
11.2
作者：
Andringa, KK;Coleman, NC;Spitz, DR
通讯作者：
Spitz, DR
DOI：
10.1016/s0360-3016(01)01534-6
发表时间：
2001-07-15
影响因子：
7
作者：
Dwarkanath, BS;Zolzer, F;Jain, V
通讯作者：
Jain, V
影响因子：
7.4
作者：
Arnér, ESJ;Nakamura, H;Spyrou, G
通讯作者：
Spyrou, G
影响因子：
6.4
作者：
Alexandre, Jerome;Batteux, Frederic;Goldwasser, Francois
通讯作者：
Goldwasser, Francois