Renal cell carcinoma and oxidative stress: The lack of peroxisomes

Frederiks, Wilma M.; Bosch, K. S.; Hoeben, Kees A.; Marle, J. van; Langbein, Sigrun

doi:10.1016/j.acthis.2009.03.003

Cited by 61 publications

(41 citation statements)

References 36 publications

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“…Interestingly, whereas proximal tubules of normal human kidney contain large numbers of peroxisomes, these organelles seem to be entirely absent in renal cancer cells. The absence of peroxisomes and mitochondrial disturbances in renal cancer cells result in alterations of fatty acid metabolism that may serve as potential targets for future therapeutic interventions (28,29).…”

Section: Renal Cancermentioning

confidence: 99%

Peroxisomes and Kidney Injury

Vasko

2016

Antioxidants & Redox Signaling

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Significance: Peroxisomes are organelles present in most eukaryotic cells. The organs with the highest density of peroxisomes are the liver and kidneys. Peroxisomes possess more than fifty enzymes and fulfill a multitude of biological tasks. They actively participate in apoptosis, innate immunity, and inflammation. In recent years, a considerable amount of evidence has been collected to support the involvement of peroxisomes in the pathogenesis of kidney injury. Recent Advances: The nature of the two most important peroxisomal tasks, betaoxidation of fatty acids and hydrogen peroxide turnover, functionally relates peroxisomes to mitochondria. Further support for their communication and cooperation is furnished by the evidence that both organelles share the components of their division machinery. Until recently, the majority of studies on the molecular mechanisms of kidney injury focused primarily on mitochondria and neglected peroxisomes. Critical Issues: The aim of this concise review is to introduce the reader to the field of peroxisome biology and to provide an overview of the evidence about the contribution of peroxisomes to the development and progression of kidney injury. The topics of renal ischemia-reperfusion injury, endotoxin-induced kidney injury, diabetic nephropathy, and tubulointerstitial fibrosis, as well as the potential therapeutic implications of peroxisome activation, are addressed in this review. Future Directions: Despite recent progress, further studies are needed to elucidate the molecular mechanisms induced by dysfunctional peroxisomes and the role of the dysregulated mitochondria-peroxisome axis in the pathogenesis of renal injury. Antioxid. Redox Signal. 25, 217-231.

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Section: Renal Cancermentioning

confidence: 99%

Peroxisomes and Kidney Injury

Vasko

2016

Antioxidants & Redox Signaling

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“…The tumorigenicity of oxidative stress has been observed among various carcinomas, especially in RCC cells, which possess low antioxidant capacities as a consequence of the absence of peroxisomes and the changed redox status (20,21). The defective antioxidant capacity also produces a prooxidant environment in RCC cells and promotes the process of renal tumor genesis (20,22).…”

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confidence: 99%

Ectopic Expression of Human MutS Homologue 2 on Renal Carcinoma Cells Is Induced by Oxidative Stress with Interleukin-18 Promotion via p38 Mitogen-activated Protein Kinase (MAPK) and c-Jun N-terminal Kinase (JNK) Signaling Pathways

Chen

Dai

Kang

et al. 2012

Journal of Biological Chemistry

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Background: Ectopically expressed MutS homologue 2 (hMSH2) is a ligand of ␥␦ T cells. Results: Oxidative stress induces ectopic expression of hMSH2 on renal carcinoma cells with IL-18 promotion via p38 MAPK and JNK pathways, promoting ␥␦ T cell-mediated lysis of renal tumor cells. Conclusion: Ectopically expressed hMSH2 is induced under stressful conditions. Significance: We reveal a mechanism of ectopic hMSH2 expression and its contribution to ␥␦ T cell-mediated immunosurveillance in stress.

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“…[30] Renal cell carcinoma is marked by substantial changes to redox homeostasis such that oxidative stress has an important role in the growth and development of this type of cancer. [31,32] Reactive oxygen-activated DNA-modifying agents directly contradict the paradigm that they cannot be designed without high levels of nonspecific reactivity, as the agents synthesized in this work do show selective cytotoxicity.…”

Section: Discussionmentioning

confidence: 79%

Oxidatively Activated DNA‐Modifying Agents for Selective Cytotoxicity

Bell

Merino

2011

ChemMedChem

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DNA-modifying agents are stalwarts of chemotherapeutic cancer treatments, but require significant design improvements to improve selectivity, minimize side effects, and for their widespread use to continue. Herein we present a novel design strategy in which DNA-modifying agents contain an oxidizable leaving group and a nitrogen mustard. The agents form strong electrophiles specifically when oxidized. Activation, measured by hydrolysis, illustrates that oxidants increase reactivity 1700-fold. Reaction in the presence of 2'-deoxyguanosine leads to the formation of lesions. Cytotoxicity measured in HeLa cells showed that low IC(50) values require an oxidizable hydroquinone and a nitrogen mustard fragment. Cytotoxicity measurements in 15 cancer cell lines demonstrates that oxidatively activated DNA-modifying agents are highly selective, as the analogue tested has IC(50) values less than 10 μM for only three of the 15 cell lines; in contrast, cisplatin is highly toxic to 13 of the 15 cell lines. The selective cytotoxicity of oxidatively activated DNA-damaging agents could be useful against kidney cancer cells, as the 786-O cell line model assay resulted in an IC(50) value of 5 μM.

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Renal cell carcinoma and oxidative stress: The lack of peroxisomes

Cited by 61 publications

References 36 publications

Peroxisomes and Kidney Injury

Peroxisomes and Kidney Injury

Ectopic Expression of Human MutS Homologue 2 on Renal Carcinoma Cells Is Induced by Oxidative Stress with Interleukin-18 Promotion via p38 Mitogen-activated Protein Kinase (MAPK) and c-Jun N-terminal Kinase (JNK) Signaling Pathways

Oxidatively Activated DNA‐Modifying Agents for Selective Cytotoxicity

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