A cohort of supporting metabolic enzymes is coinduced with nitric oxide synthase in human tumor cell lines

Andreas K. Nussler, Zhi Ze Liu, Kazuyuki Hatakeyama, David A. Geller, Timothy R. Billiar, Sidney M. Morris*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Although nitric oxide (NO) has cytotoxic activity against certain tumor cell lines, some human tumor cell lines can themselves produce NO by expressing the inducible isoform of NO synthase (iNOS). As rates of cellular NO synthesis play a major role in determining whether NO has cytotoxic or cytoprotective effects at anatomic sites of NO production, identification of cellular processes which regulate rates of NO synthesis by iNOS is important for understanding the role of NO in tumor cell biology. This study demonstrates that argininosuccinate synthetase and GTP-cyclohydrolase-I, which catalyze rate-limiting steps in the synthesis of iNOS substrate (arginine) and cofactor (tetrahydrobiopterin), respectively, are coinduced with iNOS expression in two human tumor cell lines. These results indicate that coinduction of these supporting metabolic pathways helps to maximize cellular NO synthesis by iNOS in human tumor cells, suggesting that these pathways might be useful targets for pharmacologic intervention in NO-producing human tumor cells.

Original languageEnglish
Pages (from-to)79-84
Number of pages6
JournalCancer Letters
Volume103
Issue number1
DOIs
StatePublished - 15 May 1996
Externally publishedYes

Keywords

  • Arginine
  • Cytokines
  • Human tumor
  • Nitric oxide

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