Increased chemosensitivity and elevated reactive oxygen species are mediated by glutathione reduction in glutamine deprived neuroblastoma cells

Izaki, Sakurako; Goto, Hiroaki; Yokota, Shumpei

doi:10.1007/s00432-007-0338-2

Cited by 14 publications

(7 citation statements)

References 23 publications

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“…33-35,39-41 As with all cancer cell types studied thus far, neuroblastoma cells also demonstrate significantly greater susceptibility to the cytotoxic effects of 2DG, relative to non-transformed cells of a similar developmental derivation. These results continue to support the hypothesis that the biochemical approach of antagonizing glucose and hydroperoxide metabolism for selectively enhancing oxidative stress for the purpose of improving cancer therapy responses, 13-17,24,32,40,42-44,46 appears to represent a promising new strategy that can be applied to developing novel combined modality cancer therapies for the treatment of neuroblastoma.…”

Section: Discussionmentioning

confidence: 89%

“…These results further suggest that inhibitors of glucose and hydroperoxide metabolism may represent a useful adjuvant for sensitizing neuroblastomas to conventional chemo-therapy agents thought to induce oxidative stress. 33-35,40 …”

Section: Discussionmentioning

confidence: 99%

“…These results continue to support the hypothesis that the biochemical approach of antagonizing glucose and hydroperoxide metabolism for selectively enhancing oxidative stress for the purpose of improving cancer therapy responses, 13-17,24,32,40,42-44,46 appears to represent a promising new strategy that can be applied to developing novel combined modality cancer therapies for the treatment of neuroblastoma. 27,33-35,41 …”

Section: Discussionmentioning

confidence: 99%

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2-deoxy-D-glucose induces oxidative stress and cell killing in human neuroblastoma cells

Shutt¹,

O’Dorisio²,

Aykin-Burns³

et al. 2010

Cancer Biology & Therapy

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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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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

2-deoxy-D-glucose induces oxidative stress and cell killing in human neuroblastoma cells

Shutt¹,

O’Dorisio²,

Aykin-Burns³

et al. 2010

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

“…In a former study, glutamine deprivation also decrease the GSH levels of neuroblastoma cells, leading to altered redox balance, impaired cell proliferation and increased chemosensitivity to the alkylating agent L-PAM. 112 Finally, the combined inhibition of GLS1 and heat-shock protein 90 induced synthetic lethality in cancer cells and mouse embryonic fibroblasts with activating alterations of the mTORC1 pathway through increased ER stress and disruption of the redox balance caused by GSH depletion. 83 Taken together, these studies underline the importance of glutamine in the maintenance of redox balance, cell growth and cell survival of both solid and hematologic tumors, setting the rational for therapeutic approaches aimed at the manipulation of glutamine metabolism to block malignancy.…”

Section: Metabolic Pathways Involved In Ros Homeostasis In Cancer Cellsmentioning

confidence: 99%

ROS homeostasis and metabolism: a dangerous liason in cancer cells

2016

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Tumor cells harbor genetic alterations that promote a continuous and elevated production of reactive oxygen species. Whereas such oxidative stress conditions would be harmful to normal cells, they facilitate tumor growth in multiple ways by causing DNA damage and genomic instability, and ultimately, by reprogramming cancer cell metabolism. This review outlines the metabolic-dependent mechanisms that tumors engage in when faced with oxidative stress conditions that are critical for cancer progression by producing redox cofactors. In particular, we describe how the mitochondria has a key role in regulating the interplay between redox homeostasis and metabolism within tumor cells. Last, we will discuss the potential therapeutic use of agents that directly or indirectly block metabolism.

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“…93 Deprivation of glutamine through the inhibition of GLS1 decreases the GSH level to alter the redox balance and increase chemosensitivity in cancer cells. 92, 94 There are other reports that inhibition of the redox pathway can effectively eradicate cancer cells. NOV-002 and canfosfamide targeting S-glutathionylation, PX-12 targeting thioredoxin and arsenic derivatives with unknown mechanisms demonstrated anti-cancer activity by increasing oxidative stress.…”

Section: Targeting Metabolism In Cancer Cellsmentioning

confidence: 99%

ROS homeostasis and metabolism: a critical liaison for cancer therapy

Kim

Bae³

2016

Exp Mol Med

244

147

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Evidence indicates that hypoxia and oxidative stress can control metabolic reprogramming of cancer cells and other cells in tumor microenvironments and that the reprogrammed metabolic pathways in cancer tissue can also alter the redox balance. Thus, important steps toward developing novel cancer therapy approaches would be to identify and modulate critical biochemical nodes that are deregulated in cancer metabolism and determine if the therapeutic efficiency can be influenced by changes in redox homeostasis in cancer tissues. In this review, we will explore the molecular mechanisms responsible for the metabolic reprogramming of tumor microenvironments, the functional modulation of which may disrupt the effects of or may be disrupted by redox homeostasis modulating cancer therapy.

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Increased chemosensitivity and elevated reactive oxygen species are mediated by glutathione reduction in glutamine deprived neuroblastoma cells

Abstract: Glutamine deprivation decreased cell proliferation and enhances cell chemosensitivity in neuroblastoma, which is presumably associated with GSH depletion.

Cited by 14 publications

References 23 publications

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

ROS homeostasis and metabolism: a dangerous liason in cancer cells

ROS homeostasis and metabolism: a critical liaison for cancer therapy

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