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Influence of glutamine on the growth of human glioma and medulloblastoma in culture.

Publication ,  Journal Article
Dranoff, G; Elion, GB; Friedman, HS; Campbell, GL; Bigner, DD
Published in: Cancer Res
September 1985

Cellular supply of glutamine, an essential substrate for growth, is derived from extracellular fluid and de novo synthesis. We investigated the relative importance of these sources to the growth of six human anaplastic glioma- and one human medulloblastoma-derived permanent cell lines. Exogenous glutamine was limiting for the proliferation of glioma-derived lines D-54 MG, U-118 MG, and U-251 MG. In contrast, medulloblastoma-derived line TE-671 and glioma-derived lines U-373 MG, D-245 MG, and D-259 MG grew in the absence of supplemental glutamine. Two cell lines with contrasting glutamine requirements, D-54 MG and TE-671, were used to explore the pharmacological interference with glutamine metabolism. DL-alpha-Aminoadipic acid, a reported glutamic acid analogue with gliotoxic properties, significantly inhibited the growth of both lines. These effects were reversed by increasing glutamine, suggesting that the major action of DL-alpha-aminoadipic acid is as a glutamine antagonist. In contrast, the glutamine synthetase inhibitor delta-hydroxylysine demonstrated activity only against TE-671. Acivicin and 6-diazo-5-oxo-L-norleucine, glutamine analogues available for clinical use, reduced the proliferation of both cell lines at pharmacological concentrations. Methionine sulfoximine, a glutamine synthetase inhibitor previously used clinically, produced marked growth inhibition only against TE-671. These findings indicate that the synthesis and utilization of glutamine are potentially exploitable targets for the chemotherapy of some human gliomas and medulloblastomas.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

September 1985

Volume

45

Issue

9

Start / End Page

4077 / 4081

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Medulloblastoma
  • Hydroxylysine
  • Humans
  • Glutamine
  • Glutamate-Ammonia Ligase
  • Glioma
  • Dose-Response Relationship, Drug
  • Diazooxonorleucine
  • Cells, Cultured
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dranoff, G., Elion, G. B., Friedman, H. S., Campbell, G. L., & Bigner, D. D. (1985). Influence of glutamine on the growth of human glioma and medulloblastoma in culture. Cancer Res, 45(9), 4077–4081.
Dranoff, G., G. B. Elion, H. S. Friedman, G. L. Campbell, and D. D. Bigner. “Influence of glutamine on the growth of human glioma and medulloblastoma in culture.Cancer Res 45, no. 9 (September 1985): 4077–81.
Dranoff G, Elion GB, Friedman HS, Campbell GL, Bigner DD. Influence of glutamine on the growth of human glioma and medulloblastoma in culture. Cancer Res. 1985 Sep;45(9):4077–81.
Dranoff, G., et al. “Influence of glutamine on the growth of human glioma and medulloblastoma in culture.Cancer Res, vol. 45, no. 9, Sept. 1985, pp. 4077–81.
Dranoff G, Elion GB, Friedman HS, Campbell GL, Bigner DD. Influence of glutamine on the growth of human glioma and medulloblastoma in culture. Cancer Res. 1985 Sep;45(9):4077–4081.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

September 1985

Volume

45

Issue

9

Start / End Page

4077 / 4081

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Medulloblastoma
  • Hydroxylysine
  • Humans
  • Glutamine
  • Glutamate-Ammonia Ligase
  • Glioma
  • Dose-Response Relationship, Drug
  • Diazooxonorleucine
  • Cells, Cultured