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A combination of 2-deoxy-d-glucose and 6-aminonicotinamide induces cell cycle arrest and apoptosis selectively in irradiated human malignant cells

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Tumor Biology

Abstract

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 mitochondrial dysfunction and non-coordinated expression of antioxidant defense, besides inhibition of repair and recovery. In the present study, our objective was to study, in a panel of human malignant cells of various origins (lung carcinoma, squamous carcinoma, oral carcinoma, and glioblastoma), if the inhibitory activity of combination (2-DG+6-AN+2Gy) against tumor growth could be considered a general phenomenon and to determine its effect on the cell cycle. The results revealed that combination (2-DG+6-AN+2Gy) treatment result in significant cell growth inhibition and induced ROS generation in all cancer cells studied. The anti-proliferative effect was related to the ability of combination (2-DG+6-AN+2Gy) to provoke growth inhibition at the G2/M arrest and apoptosis. Furthermore, combination (2-DG+6-AN+2Gy) induced G2/M arrest is closely correlated to decreased cyclin A, cyclin B1, and cdc2 levels.

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Abbreviations

2-DG:

2-Deoxy-d-glucose

6-AN:

6-Aminonicotinamide

ROS:

Reactive oxygen species

PPP:

Pentose phosphate pathway

DCFH-DA:

5,6-Carboxy-2′,7′-dichlorofluoresceindiacetate

FITC:

Fluorescein isothiocyanate

PI:

Propidium iodide

PBS:

Phosphate buffered saline

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Acknowledgments

We are thankful to Dr. RP Tripathi, Director, Institute of Nuclear Medicine and Allied Sciences for his support. We also thank Mrs. Namita Kalra for her help in flow cytometry experiments. The authors alone are responsible for the content and writing of the paper.

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Correspondence to Rajeev Varshney.

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Bhardwaj, R., Sharma, P.K., Jadon, S.P.S. et al. A combination of 2-deoxy-d-glucose and 6-aminonicotinamide induces cell cycle arrest and apoptosis selectively in irradiated human malignant cells. Tumor Biol. 33, 1021–1030 (2012). https://doi.org/10.1007/s13277-012-0335-1

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  • DOI: https://doi.org/10.1007/s13277-012-0335-1

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