title: A combination of 2-deoxy-D-glucose and 6-aminonicotinamide induces oxidative stress mediated selective radiosensitization of malignant cells via mitochondrial dysfunction.
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.
authors.affiliation: Institute of Nuclear Medicine and Allied Sciences, DRDO, Brig S K Mazumdar Road, Delhi, 110 054, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Bhardwaj
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Sharma
authors.forename: Suryaprakash Singh
authors.initials: SS
authors.lastname: Jadon
authors.forename: Rajeev
authors.initials: R
authors.lastname: Varshney
mesh_terms: D015120:6-Aminonicotinamide / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000494:pharmacology*; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D008928:Mitochondria / Q000187:drug effects* / Q000528:radiation effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
chemical_list: D011838:Radiation-Sensitizing Agents; D015120:6-Aminonicotinamide; D003847:Deoxyglucose