p53 is an important factor for the radiosensitization effect of 2-deoxy-D-glucose

  • Authors: Chompunoot Sinthupibulyakit, Kristopher R. Grimes, Frederick E. Domann, Yong Xu, Fang Fang, Wanida Ittarat, Daret K. St. Clair, William St. Clair
  • View Affiliations

  • Published online on: Tuesday, September 1, 2009
  • Pages: 609-615
  • DOI: 10.3892/ijo_00000372

Abstract

Metabolic change in cancer cells by preferential production of energy through glycolysis is a well-documented characteristic of cancer. However, whether inhibition of glycolysis will enhance the efficacy of radiation therapy is a matter of debate. In this study which uses lung cancer as the model, we demonstrate that the improvement of radiotherapy by 2-deoxy-D-glucose (2DG) is p53-dependent. Based on clonogenic survival data, we show that p53-deficient lung cancer cells (H358) are more sensitive to 2DG treatment when compared to p53 wild-type lung cancer cells (A549). The effective doses of 2DG at 0.5-surviving fraction of A549 and H358 are 17.25 and 4.61 mM, respectively. Importantly, 2DG exhibits a significant radiosensitization effect in A549 cells but not in H358 cells. Treatment with 2DG increases radiation-induced p53 protein levels in A549 cells. siRNA inhibition of p53 in A549 cells reduces the radiosensitization effect of 2DG. Furthermore, ectopic expression of wild-type p53 in H358 cells significantly enhances the radiosensitization effect of 2DG as determined by colony formation assay. In nude mice injected with A549 cells, treatment of 2DG enhances the efficacy of radiation therapy. Together, these results suggest that inhibition of glycolysis may only be beneficial for radiation therapy of cancer expressing wild-type p53.
Journal Cover

September 2009
Volume 35 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Sinthupibulyakit, C., Grimes, K., Domann, F., Xu, Y., Fang, F., Ittarat, W., St. Clair, D., & St. Clair, W. (2009). p53 is an important factor for the radiosensitization effect of 2-deoxy-D-glucose. International Journal of Oncology, 35(3), 609-615.
MLA
Sinthupibulyakit, Grimes, Domann, Xu, Fang, Ittarat, St. Clair, and William St. Clair. "p53 is an important factor for the radiosensitization effect of 2-deoxy-D-glucose." International Journal of Oncology International Journal of Oncology 35.3 (2009): 609-615.
Chicago
Sinthupibulyakit, Grimes, Domann, Xu, Fang, Ittarat, St. Clair, and William St. Clair. "p53 is an important factor for the radiosensitization effect of 2-deoxy-D-glucose." International Journal of Oncology International Journal of Oncology 35 no. 3 (2009): 609-615.