2-DEOXY-D-GLUCOSE PREFERENTIALLY KILLS MULTIDRUG-RESISTANT HUMAN KB CARCINOMA CELL-LINES BY APOPTOSIS

The aim of this study was to determine the mechanism of cell death ass ociated with the preferential killing df multidrug-resistant (MDR) cel ls by the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in a range of M DR human KB carcinoma cell lines selected in different drugs. The D-10 values for KB-V1, KB-C1 and KB-A1 (selected in vinblastine;colchicine and doxorubicin respectively) were 1.74, 1.04 and 0.31 mM, respective ly, compared with 4.60 mM for the parental cell line (KB-3-1). The mec hanism of cell death was identified as apoptosis, based on nuclear mor phology, annexin V binding and poly(ADP-ribose) polymerase (PARP) clea vage. 2DG induced apoptosis in the three MDR cell lines in a dose- and time-dependent manner and did not induce necrosis. PARP cleavage was detected in KB-CI cells within 2 h of exposure to 50 mM 2DG and slight ly later in KB-A1 and KB-V1 cells. The relative levels of 2DG sensitiv ity did not correlate with the levels of multidrug resistance or with the reduced levels of the glucose transporter GLUT-1 in these cells. W e speculate that a 2DG-stimulated apoptotic pathway in MDR KB cells di ffers from that in normal KB cells.