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

Chompunoot Sinthupibulyakit; Kristopher R Grimes; Frederick E Domann; Yong Xu; Fang Fang; Wanida Ittarat; Daret K St Clair; William St Clair

doi:10.3892/ijo_00000372

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

Journal article

Open access

Peer reviewed

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

Chompunoot Sinthupibulyakit, Kristopher R Grimes, Frederick E Domann, Yong Xu, Fang Fang, Wanida Ittarat, Daret K St Clair and William St Clair

International journal of oncology, Vol.35(3), pp.609-615

09/2009

DOI: 10.3892/ijo_00000372

PMCID: PMC2805438

PMID: 19639181

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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.

Lung Neoplasms - genetics

Humans

Lung Neoplasms - metabolism

Tumor Suppressor Protein p53 - metabolism

Radiation Tolerance - genetics

Lung Neoplasms - therapy

Glycolysis - drug effects

Blotting, Western

Tumor Suppressor Protein p53 - genetics

Radiation Tolerance - drug effects

Xenograft Model Antitumor Assays

Animals

Mice, Nude

Deoxyglucose - pharmacology

Cell Line, Tumor

Female

Mice

RNA, Small Interfering

Antimetabolites - pharmacology

Details

Title: Subtitle: p53 is an important factor for the radiosensitization effect of 2-deoxy-D-glucose
Creators: Chompunoot Sinthupibulyakit - Graduate Center for Toxicology, University of Kentucky, Lexington, KY, USA
Kristopher R Grimes
Frederick E Domann
Yong Xu
Fang Fang
Wanida Ittarat
Daret K St Clair
William St Clair
Resource Type: Journal article
Publication Details: International journal of oncology, Vol.35(3), pp.609-615
Publisher: Greece
DOI: 10.3892/ijo_00000372
PMID: 19639181
PMCID: PMC2805438
ISSN: 1019-6439
eISSN: 1791-2423
Grant note: R01 CA049797 / NCI NIH HHS CA 049797 / NCI NIH HHS R01 CA115801-03 / NCI NIH HHS CA 115801 / NCI NIH HHS R01 CA115801 / NCI NIH HHS
Language: English
Date published: 09/2009
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984047758602771

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