Tumor Biology

, Volume 33, Issue 4, pp 1021–1030 | Cite as

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

  • Richa Bhardwaj
  • Pradeep K. Sharma
  • S. P. S. Jadon
  • Rajeev Varshney
Research Article

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.

Keywords

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

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

Supplementary material

13277_2012_335_MOESM1_ESM.doc (90 kb)
ESM 1(DOC 90 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Richa Bhardwaj
    • 1
  • Pradeep K. Sharma
    • 1
    • 2
  • S. P. S. Jadon
    • 3
  • Rajeev Varshney
    • 1
    • 4
  1. 1.Institute of Nuclear Medicine and Allied Sciences, DRDODelhiIndia
  2. 2.School of BiotechnologyGuru Gobind Singh Indraprastha UniversityDwarkaIndia
  3. 3.Department of ChemistryShri Varshneya CollegeAligarhIndia
  4. 4.DRDO Bhawan, Defence Research and Development Organisation, Ministry of DefenceGovernment of IndiaNew DelhiIndia

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