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

作者：Bhardwaj Richa; Sharma Pradeep K; Jadon S P S; Varshney Rajeev^*

来源：Tumor Biology, 2012, 33(4): 1021-1030.

DOI：10.1007/s13277-012-0335-1

• Radiosensitization
• 2-Deoxy-D-glucose
• 6-Aminonicotinamide
• Oxidative stress
• G2/M arrest

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.

• 出版日期2012-8