2-deoxy-D-glucose induces oxidative stress and cell killing in human neuroblastoma cells.
2-deoxy-D-glucose induces oxidative stress and cell killing in human neuroblastoma cells.
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DOI：
10.4161/cbt.9.11.11632
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发表时间：
2010-06-01
影响因子：
3.6
通讯作者：
Spitz DR
中科院分区：
文献类型：
--
作者：
Shutt DC;O'Dorisio MS;Aykin-Burns N;Spitz DR
恶性细胞对葡萄糖剥夺诱导的细胞毒性的敏感性明显高于正常细胞（Biochem J 418：29）。据推测，这是由于癌细胞中活性氧（RO）的产生水平较高，导致对葡萄糖代谢产生的还原当量的需求增加，以使氢过氧化物解毒。由于体内不能实现完全的葡萄糖剥夺，因此已经提出拮抗葡萄糖代谢的试剂，例如2-脱氧-D-葡萄糖（2DG），可以模拟体外葡萄糖剥夺，其通过氧化应激选择性地杀死癌细胞。为了验证这一假设，神经母细胞瘤细胞系与2DG和克隆生存的影响和生存的集落中的细胞表型的分布进行了测定。结果表明，神经母细胞瘤中发现的所有三种主要细胞类型（雪旺氏细胞、神经元细胞和中间细胞）对2DG诱导的克隆源性细胞杀伤敏感。此外，巯基抗氧化剂，N-乙酰半胱氨酸，或与聚乙二醇结合的超氧化物歧化酶和过氧化氢酶的治疗，保护神经母细胞瘤细胞从2DG诱导的细胞杀伤。最后，与神经母细胞瘤细胞系相比，正常的非永生化神经前体细胞对2DG诱导的细胞杀伤具有相对抗性。这些结果支持了这样的假设，即葡萄糖代谢抑制剂可以通过选择性地增强代谢性氧化应激而成为治疗神经母细胞瘤的有用佐剂。
Malignant cells have a demonstrably greater sensitivity to glucose deprivation-induced cytotoxicity than normal cells (Biochem J 418:29). This has been hypothesized to be due to a higher level of reactive oxygen species (ROs) production in cancer cells leading to the increased need for reducing equivalents, produced by glucose metabolism, to detoxify hydroperoxides. Because complete glucose deprivation cannot be achieved in vivo, it has been proposed that agents that antagonize glucose metabolism, such as 2-deoxy-D-glucose (2DG), can mimic in vitro glucose deprivation that selectively kills cancer cells by oxidative stress. To test this hypothesis, neuroblastoma cell lines were treated with 2DG and the effects on clonogenic survival and the distribution of cellular phenotypes among surviving colonies was determined. The results showed that all three major cell types found in neuroblastoma (schwann, Neuronal and Intermediate) were sensitive to 2DG-induced clonogenic cell killing. Furthermore, treatment with the thiol antioxidant, N-acetyl cysteine, or with polyethylene glycol-conjugated superoxide dismutase and catalase, protected neuroblastoma cells from 2DG-induced cell killing. Finally normal non-immortalized neural precursor cells were relatively resistant to 2DG-induced cell killing when compared to neuroblastoma cell lines. These results support the hypothesis that inhibitors of glucose metabolism could represent useful adjuvants in the treatment of neuroblastoma by selectively enhancing metabolic oxidative stress.
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影响因子：
--
作者：
Acosta S;Lavarino C;Paris R;Garcia I;de Torres C;Rodríguez E;Beleta H;Mora J
通讯作者：
Mora J
影响因子：
11.2
作者：
Ara T;Song L;Shimada H;Keshelava N;Russell HV;Metelitsa LS;Groshen SG;Seeger RC;DeClerck YA
通讯作者：
DeClerck YA
影响因子：
2.9
作者：
Liu, H;Hu, YP;Lampidis, TJ
通讯作者：
Lampidis, TJ
影响因子：
9.7
作者：
Ross, RA;Biedler, JL;Spengler, BA
通讯作者：
Spengler, BA
影响因子：
15.9
作者：
AW, TY;RHOADS, CA
通讯作者：
RHOADS, CA