Glucose deprivation-induced cytotoxicity in drug resistant human breast carcinoma MCF-7/ADR cells: role of c-myc and bcl-2 in apoptotic cell death.
We investigated the effect of glucose deprivation treatment on clonogenicity in multidrug-resistant human breast carcinoma MCF-7/ADR cells. Survival of MCF-7/ADR cells decreased exponentially up to 8 hours of incubation in the glucose-free medium. The surviving fraction of these cells for 8 hours of glucose-deprivation treatment was 1.5 x 10(-3). Photomicrographs and gel electrophoresis data suggest that glucose deprivation-induced cell death is associated with apoptosis. Data from western and northern blots showed an induction of c-myc gene expression during treatment with glucose-free medium in MCF-7/ADR cells. MCF-7/ADR cells transfected with c-myc antisense oligodeoxynucleotides became resistant to glucose deprivation-induced apoptosis. Overexpression of bcl-2 gene protected MCF-7/ADR cells from this apoptotic cell death. Taken together, these results indicate that c-myc expression is a necessary component of glucose-free medium induced apoptosis and bcl-2 prevents apoptotic death induced by c-myc.
Lee
Y J
YJ
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073, USA.
Galoforo
S S
SS
Berns
C M
CM
Tong
W P
WP
Kim
H R
HR
Corry
P M
PM
D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms / Q000473:pathology*; D002470:Cell Survival; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2; D016259:Genes, myc; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D014407:Tumor Cells, Cultured
D005947:Glucose