2-DEOXYGLUCOSE INHIBITS CHEMOTHERAPEUTIC DRUG-INDUCED APOPTOSIS IN HUMAN MONOCYTIC LEUKEMIA U937 CELLS WITH INHIBITION OF C-JUN N-TERMINAL KINASE-1 STRESS-ACTIVATED PROTEIN-KINASE ACTIVATION

Human monocytic leukemia U937 cells undergo apoptosis when treated wit h antitumor drugs, such as etoposide, camptothecin and mitomycin C, Th e molecular mechanism of the drug-induced apoptosis is not well unders tood. In this study, we found that 2-deoxyglucose (2DG), an analog of D-glucose and an inducer of glucose-regulated stress, inhibited antica ncer drug-induced but not tumor necrosis factor-alpha-induced apoptosi s of U937 cells. 2DG did not reduce initial cellular damage caused by etoposide, an inhibitor of topoisomerase II, suggesting that 2DG affec ted subsequent cellular responses involved in apoptosis. 2DG inhibited the etoposide-induced activation of c-Jun N-terminal kinase 1/stress- activated protein kinase (JNK1/SAPK) and the subsequent activation of CPP32, both of which are positive regulators for etoposide-induced apo ptosis of U937 cells, Our results indicate that 2DG inhibits apoptosis by blocking the signals from cellular DNA damage for JNK1/SAPK activa tion. (C) 1998 Wiley-Liss, Inc.