S-nitrosoglutathione and hypoxia-inducible factor-1 confer chemoresistance against carbamoylating cytotoxicity of BCNU in rat C6 glioma cells

Ding I. Yang, Shang Der Chen, Jiu Haw Yin, Chung Y. Hsu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

BCNU (1,3-bis[2-chloroethyl]-1-nitrosourea) is the mainstay in glioblastoma multiform chemotherapy with only minimal effects. BCNU may kill tumor cells via carbamoylating cytotoxicity, which irreversibly inhibits glutathione reductase with resultant accumulation of oxidized form of glutathione causing oxidative stress. S-nitrosoglutathione (GSNO) is a product of glutathione and nitric oxide interaction. We report that GSNO formation may underlie carbamoylating Chemoresistance mediated by activation of inducible nitric oxide synthase. Transactivation of hypoxia-inducible factor-1 (HIF-1)-responsive genes reduces oxidative stress caused by glutathione depletion. We also noted that preconditioning of C6 glioma cells to induce HIF-1 and its downstream genes confers Chemoresistance against carbamoylating cytotoxicity of BCNU.

Original languageEnglish
Pages (from-to)229-234
Number of pages6
JournalAnnals of the New York Academy of Sciences
Volume1042
DOIs
Publication statusPublished - 2005

Keywords

  • Alkylation
  • Carbamoylation
  • Chemoresistance
  • Chemotherapy
  • Hypoxia
  • iNOS
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Fingerprint Dive into the research topics of 'S-nitrosoglutathione and hypoxia-inducible factor-1 confer chemoresistance against carbamoylating cytotoxicity of BCNU in rat C6 glioma cells'. Together they form a unique fingerprint.

  • Cite this