This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhu, Z. Articles by Thompson, H. J. Search for Related Content PubMed PubMed Citation Articles by Zhu, Z. Articles by Thompson, H. J. Related Collections Preclinical Intervention Preclinical Intervention: In Vitro: Drugs, Mechanisms Preclinical Intervention: In Vivo (Animals): Drugs, Nutritional Interventions, Mechanisms

2-Deoxyglucose as an Energy Restriction Mimetic Agent: Effects on Mammary Carcinogenesis and on Mammary Tumor Cell Growth In vitro

Cancer Prevention Laboratory, Colorado State University, Fort Collins, Colorado

Requests for reprints: Henry J. Thompson, Cancer Prevention Laboratory, Colorado State University, 1173 Campus Delivery, Fort Collins, CO 80523. Phone: 970-491-7748; Fax: 970-491-3542; E-mail: henry.thompson{at}colostate.edu.

Dietary energy restriction (DER) is a potent inhibitor of carcinogenesis, but chronic DER in human populations is difficult to sustain. Consequently, interest exists in identifying energy restriction mimetic agents (ERMAs), agents that provide the health benefits of DER without reducing caloric intake. The selection of a candidate ERMAs for this study was based on evidence that DER inhibits carcinogenesis by limiting glucose availability. The study objective was to determine if 2-deoxyglucose (2-DG), a glucose analogue that blocks its metabolism, would inhibit mammary carcinogenesis. Pilot studies were done to establish a dietary concentration of 2-DG that would not affect growth. For the carcinogenesis study, ninety 21-day-old female Sprague-Dawley rats were injected i.p. with 50 mg of 1-methyl-1-nitrosourea per kilogram of body weight. Following injection, animals were ad libitum fed AIN-93G diet containing 0.00%, 0.02%, or 0.03% (w/w) 2-DG for 5 weeks. 2-DG decreased the incidence and multiplicity of mammary carcinomas and prolonged cancer latency (P < 0.05). The 0.02% dose of 2-DG had no effect on circulating levels of glucose, insulin, insulin-like growth factor-I, IGF binding protein-3, leptin, or body weight gain. Using MCF-7 human breast cancer cells to investigate the signaling pathways perturbed by disruption of glucose metabolism, 2-DG reduced cell growth and intracellular ATP in a dose- and time-dependent manner (P < 0.01). Treatment with 2-DG increased levels of phosphorylated AMP-activated protein kinase and Sirt-1 and reduced phosphorylated Akt (P < 0.05). These studies support the hypothesis that DER inhibits carcinogenesis, in part, by limiting glucose availability and that energy metabolism is a target for the development of ERMA for chemoprevention.

This article has been cited by other articles:

				H. Wu, H. Zhu, D. X. Liu, T.-K. Niu, X. Ren, R. Patel, W. N. Hait, and J.-M. Yang Silencing of Elongation Factor-2 Kinase Potentiates the Effect of 2-Deoxy-D-Glucose against Human Glioma Cells through Blunting of Autophagy Cancer Res., March 15, 2009; 69(6): 2453 - 2460. [Abstract] [Full Text] [PDF]

				G. P. Lobo, K. A. Waite, S. M. Planchon, T. Romigh, J. A. Houghton, and C. Eng ATP modulates PTEN subcellular localization in multiple cancer cell lines Hum. Mol. Genet., September 15, 2008; 17(18): 2877 - 2885. [Abstract] [Full Text] [PDF]

				W. Jiang, Z. Zhu, and H. J. Thompson Dietary Energy Restriction Modulates the Activity of AMP-Activated Protein Kinase, Akt, and Mammalian Target of Rapamycin in Mammary Carcinomas, Mammary Gland, and Liver Cancer Res., July 1, 2008; 68(13): 5492 - 5499. [Abstract] [Full Text] [PDF]

				D. Zhong, X. Liu, K. Schafer-Hales, A. I. Marcus, F. R. Khuri, S.-Y. Sun, and W. Zhou 2-Deoxyglucose induces Akt phosphorylation via a mechanism independent of LKB1/AMP-activated protein kinase signaling activation or glycolysis inhibition Mol. Cancer Ther., April 1, 2008; 7(4): 809 - 817. [Abstract] [Full Text] [PDF]

				Z. Zhu, W. Jiang, J. N. McGinley, J. M. Price, B. Gao, and H. J. Thompson Effects of Dietary Energy Restriction on Gene Regulation in Mammary Epithelial Cells Cancer Res., December 15, 2007; 67(24): 12018 - 12025. [Abstract] [Full Text] [PDF]

				Y.-C. Hsu, H.-C. Lee, Y.-H. Ping, T.-Y. Liu, W.-Y. Lui, and C.-W. Chi Mitochondria Are an Essential Mediator of Nitric Oxide/Cyclic Guanosine 3',5'-Monophosphate Blocking of Glucose Depletion Induced Cytotoxicity in Human HepG2 Cells Mol. Cancer Res., September 1, 2007; 5(9): 923 - 932. [Abstract] [Full Text] [PDF]

				J. L.J. Dearling, U. Qureshi, R. H.J. Begent, and R. B. Pedley Combining Radioimmunotherapy with Antihypoxia Therapy 2-Deoxy-D-Glucose Results in Reduction of Therapeutic Efficacy Clin. Cancer Res., March 15, 2007; 13(6): 1903 - 1910. [Abstract] [Full Text] [PDF]

				H. Zhang, A. M. Pelzer, D. T. Kiang, and D. Yee Down-regulation of Type I Insulin-like Growth Factor Receptor Increases Sensitivity of Breast Cancer Cells to Insulin Cancer Res., January 1, 2007; 67(1): 391 - 397. [Abstract] [Full Text] [PDF]