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 associated with the preferential killing of multidrug-resistant (MDR) cells by the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in a range of MDR human KB carcinoma cell lines selected in different drugs. The D10 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, respectively, compared with 4.60 mM for the parental cell line (KB-3-1). The mechanism of cell death was identified as apoptosis, based on nuclear morphology, annexin V binding and poly(ADP-ribose) polymerase (PARP) cleavage. 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-C1 cells within 2 h of exposure to 50 mM 2DG and slightly later in KB-A1 and KB-V1 cells. The relative levels of 2DG sensitivity did not correlate with the levels of multidrug resistance or with the reduced levels of the glucose transporter GLUT-1 in these cells. We speculate that a 2DG-stimulated apoptotic pathway in MDR KB cells differs from that in normal KB cells.
Bell
S E
SE
Department of Biology, The University of York, UK.
Quinn
D M
DM
Kellett
G L
GL
Warr
J R
JR
D000963:Antimetabolites / Q000494:pharmacology*; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D051272:Glucose Transporter Type 1; D006801:Humans; D008856:Microscopy, Fluorescence; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000963:Antimetabolites; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D003847:Deoxyglucose; D011065:Poly(ADP-ribose) Polymerases