UDP-AT-Acetylhexosamine Modulation by Glucosamine and Uridine in NCI N-417 Variant Small Cell Lung Cancer Cells: 31P Nuclear Magnetic Resonance Results

Nathanael V. Pederson, Richard H. Knop, William M. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Small cell lung cancer (SCLQ occurs as two neuroendocrine subtypes, SCLC-C (classic) and SCLC-V (variant). One reported difference is elevated levels of diphosphodiesters (DPDE) in the more differentiated SCLC-C subtype. DPDE have been identified as primarily UDP-JV-acetylhexosamines (UDP-NAH) in a variety of tumors, and changes in DPDE levels have been observed during experiments designed to induce cell differentiation. UDP-NAH synthesis is controlled by negative feedback regulation of glutamine:fructose-6-P amidotransferase (EC 2.6.1.16), which can be circumvented by glucosamine. Using 3IP nuclear magnetic resonance analysis of extracts and perfused cells, we have identified UDP-Atacetylglucosamine and UDP-A/-acetylgalactosamine as the primary metabolites in the DPDE spectral region of SCLC-V N-417 cells. Glucosamine addition causes a rapid increase in UDP-NAH levels. At glucosamine: glucose ratios of 1:1 and 10:1 formation of the UDP-NAH intermediates JV-acetylglucosamine 6-phosphate and UDP-N-acetylglucosamine 1-phosphate is also observed, indicating UTP limitation. Subsequent uridine addition results in depletion of the intermediates and increased UDP-NAH formation. Moreover, N-417 cells retain the capacity to rapidly convert uridine to UTP despite low ATP and phosphocreatine levels. This expansion of the uridine pool may represent an additional metabolic reserve not yet addressed in the design of therapy options.

Original languageEnglish (US)
Pages (from-to)3782-3786
Number of pages5
JournalCancer Research
Volume52
Issue number13
StatePublished - Jul 1992

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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