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Tumor Biology
Published in: Tumor Biology 5/2011

01-10-2011 | Research Article

A combination of 2-deoxy-d-glucose and 6-aminonicotinamide induces oxidative stress mediated selective radiosensitization of malignant cells via mitochondrial dysfunction

Authors: Richa Bhardwaj, Pradeep Kumar Sharma, Suryaprakash Singh Jadon, Rajeev Varshney

Published in: Tumor Biology | Issue 5/2011

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Abstract

Oxidative stress-mediated mitochondrial dysfunction is known to induce intrinsic pathway of apoptosis. Previously, we have shown that a combination of metabolic modifiers 2-deoxy-D-glucose (2-DG) and 6-aminonicotinamide (6-AN) results in oxidative stress-mediated radiosensitization of malignant cells via noncoordinated expression of antioxidant defense. We now show that the combination (2-DG + 6-AN + 2Gy) induces significant alterations in mitochondrial membrane potential and oxidative damage to lipid and proteins selectively in malignant cells resulting in the release of cytochrome c from mitochondria and increase in Bax/Bcl-2 ratio stimulating intrinsic pathway of apoptosis, besides enhancing the mitotic death linked to cytogenetic damage. These results highlight the role of mitochondrial dysfunction in selective radiosensitization by 2-DG + 6-AN, besides inhibition of energy-linked DNA repair processes and generation of oxidative stress reported earlier.
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Metadata
Title
A combination of 2-deoxy-d-glucose and 6-aminonicotinamide induces oxidative stress mediated selective radiosensitization of malignant cells via mitochondrial dysfunction
Authors
Richa Bhardwaj
Pradeep Kumar Sharma
Suryaprakash Singh Jadon
Rajeev Varshney
Publication date
01-10-2011
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2011
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-011-0197-y

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