Detachment of the glycolytic enzymes, phosphofructokinase and aldolase, from cytoskeleton of melanoma cells, induced by local anesthetics.
Cancer cells are characterized by a high rate of glycolysis, which is their primary energy source. An important mechanism that controls glycolysis is the reversible binding of glycolytic enzymes to cytoskeleton. We report here that the local anesthetics, lidocaine and bupivacaine, induced a dose-dependent detachment of the glycolytic enzymes, phosphofructokinase (EC 2.7.1.11) and aldolase (EC 4.1.2.13), from cytoskeleton of B16 melanoma cells. The detachment of glycolytic enzymes from cytoskeleton would reduce the provision of local ATP, in the vicinity of cytoskeleton-membrane and would also affect cytoskeleton structure. We show here that the local anesthetics decreased the viability of melanoma cells. The detachment of the glycolytic enzymes from cytoskeleton, induced by the drugs, preceded melanoma cell death, which indicates that this is an early effect and not a result of cell death. Bupivacaine was more potent than lidocaine both on the glycolytic enzymes and on cell viability. The present results suggest that local anesthetics, and especially bupivacaine, are promising drugs for the treatment of melanoma.
Schwartz
D
D
Health Sciences Research Center, Bar-Ilan University, Ramat Gan, 52900, Israel.
Beitner
R
R
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002045:Bupivacaine / Q000494:pharmacology*; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000201:enzymology*; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism*; D006019:Glycolysis; D008012:Lidocaine / Q000494:pharmacology*; D008545:Melanoma; D051379:Mice; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000779:Anesthetics, Local; D000970:Antineoplastic Agents; D008012:Lidocaine; D010732:Phosphofructokinase-1; D005634:Fructose-Bisphosphate Aldolase; D002045:Bupivacaine