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Glucose Deprivation‐Induced Oxidative Stress in Human Tumor Cells: A Fundamental Defect in Metabolism?
Author(s) -
SPITZ DOUGLAS R.,
SIM JULIA E.,
RIDNOUR LISA A.,
GALOFORO SANDRA S.,
LEE YONG J.
Publication year - 2000
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 - 10.1111/j.1749-6632.2000.tb06199.x
Subject(s) - oxidative stress , intracellular , cytotoxic t cell , signal transduction , cytotoxicity , cancer cell , microbiology and biotechnology , oxidative phosphorylation , biology , chemistry , cancer research , biochemistry , cancer , genetics , in vitro
A bstract : Recently, glucose deprivation‐induced oxidative stress has been shown to cause cytotoxicity, activation of signal transduction (i.e., ERK1, ERK2, JNK, and Lyn kinase), and increased expression of genes associated with malignancy (i.e., bFGF and c‐Myc) in MCF‐7/ADR human breast cancer cells. These results have led to the proposal that intracellular oxidation/reduction reactions involving hydroperoxides and thiols may provide a mechanistic link between metabolism, signal transduction, and gene expression in these human tumor cells. The current study shows that several other transformed human cell types appear to be more susceptible to glucose deprivation‐induced cytotoxicity and oxidative stress than untransformed human cell types. In a matched pair of normal and SV40‐transformed human fibroblasts the cytotoxic process is shown to be dependent upon ambient O 2 concentration. A theoretical model to explain the results is presented and implications to unifying modern theories of cancer are discussed.