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2-deoxy-D-glucose inhibits the antitumor effects of α-difluoromethylornithine on the growth of colon cancer in vivo

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Summary

The glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has been shown to inhibit the growth of certain cancers. α-Difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase (ODC), the ratelimiting enzyme in polyamine biosynthesis. DFMO has been shown to inhibit cancer growth in a number of models. The present study was designed to investigate the effects of 2-DG alone and combined with DFMO on MC-26 mouse colon adenocarcinoma tumors growing in vivo. Twenty-eight male Balb/c mice were inoculated with 250,000 MC-26 cells, and then randomized into four groups of 7 each: group I served as control; group II received DFMO (3% in drinking water); group III received 2-DG (500 mg/kg/d IP); group IV received a combination of 2-DG and DFMO. Treatment began 5 days after tumor cell inoculation. MC-26 tumor area was reduced 73% by DFMO compared to a 24% reduction caused by 2-DG. The tumor weight was reduced 80% by DFMO and 52% by 2-DG. The tumor contents of DNA, RNA, and protein were significantly reduced by DFMO but not 2-DG. The tumor concentration of the polyamines putrescine and spermidine were reduced by DFMO alone or combined with 2-DG while spermine levels remained unchanged. 2-DG alone did not alter polyamine levels. These results indicate that both 2-DG and DFMO, when added as single agents, inhibit tumor growth. However, the addition of 2-DG to the DFMO regimen inhibited the antitumor effects of DFMO. Survival studies performed on MC-26 cells in vitro corroborated the antagonisms between DFMO and 2-DG that were shown in vivo.

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Author information

Authors and Affiliations

  1. Department of Surgery, The University of Texas Medical Branch, Galveston, Texas, USA

    Rami Saydjari, James R. Upp Jr., Robert W. Alexander, Sam C. Barranco, Courtney M. Townsend Jr. & James C. Thompson

  2. Department of Radiation Oncology and Biophysics, Eastern Virginia Medical School, Norfolk, Virginia, USA

    Sam C. Barranco

Authors
  1. Rami Saydjari
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  2. James R. Upp Jr.
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  3. Robert W. Alexander
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  4. Sam C. Barranco
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  5. Courtney M. Townsend Jr.
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  6. James C. Thompson
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Additional information

Dr. Upp was awarded a fellowship grant from the American Cancer Society Texas Division.

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Saydjari, R., Upp, J.R., Alexander, R.W. et al. 2-deoxy-D-glucose inhibits the antitumor effects of α-difluoromethylornithine on the growth of colon cancer in vivo . Invest New Drugs 7, 131–138 (1989). https://doi.org/10.1007/BF00170849

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