Premium
S‐Nitrosoglutathione and Hypoxia‐Inducible Factor‐1 Confer Chemoresistance against Carbamoylating Cytotoxicity of BCNU in Rat C6 Glioma Cells
Author(s) -
YANG DINGI,
CHEN SHANGDER,
YIN JIUHAW,
HSU CHUNG Y.
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1338.025
Subject(s) - glutathione , cytotoxicity , chemistry , transactivation , nitric oxide , oxidative stress , glioma , s nitrosoglutathione , glutathione reductase , cancer research , pharmacology , biochemistry , transcription factor , biology , enzyme , gene , in vitro , glutathione peroxidase , organic chemistry
A bstract : 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.