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 clonoge nicity in multidrug-resistant human breast carcinoma MCF-7/ADR cells. Survival of MCF-7/ADR cells decreased exponentially up to 8 hours of i ncubation in the glucose-free medium. The surviving fraction of these cells for 8 hours of glucose-deprivation treatment was 1.5x10(-3). Pho tomicrographs and gel electrophoresis data suggest that glucose depriv ation-induced cell death is associated with apoptosis. Data from weste rn and northern blots showed an induction of c-myc gene expression dur ing treatment with glucose-free medium in MCF-7/ADR cells. MCF-7/ADR c ells transfected with c-myc antisense oligodeoxynucleotides became res istant to glucose deprivation-induced apoptosis. Overexpression of bcl -2 gene protected MCF-7/ADR cells from this apoptotic cell death. Take n together, these results indicate that c-myc expression is a necessar y component of glucose-free medium induced apoptosis and bcl-2 prevent s apoptotic death induced by c-myc.