Local anesthetics induce a decrease in the levels of glucose 1, 6-bisphosphate, fructose 1,6-bisphosphate, and ATP, and in the viability of melanoma cells.
Glycolysis is known to be the primary energy source in cancer cells. We investigated here the effect of local anesthetics, lidocaine and bupivacaine, on the levels of glucose 1,6-bisphosphate and fructose 1,6-bisphosphate, the two stimulatory signal molecules of glycolysis, and on ATP levels and cell viability in B16 melanoma cells. We found that both drugs induced a significant, dose-dependent reduction in the levels of glucose 1,6-bisphosphate, fructose 1, 6-bisphosphate, ATP, and cell viability. Bupivacaine was more potent than lidocaine. The decrease in glucose 1,6-bisphosphate and fructose 1,6-bisphosphate, induced by the local anesthetics, preceded the reduction in the viability of melanoma cells, indicating that these are early changes and not a result of cell death. Cell viability was reduced in a close correlation with the fall in ATP. These findings suggest that the fall in the levels of the two signal allosteric regulators of glycolysis, induced by the local anesthetics, is one of the mechanisms that causes a reduction in glycolysis and ATP levels, which eventually leads to melanoma cell death. These experiments suggest that local anesthetics, and especially bupivacaine, are most promising agents in the treatment of melanoma.
Karniel
M
M
Health Sciences Research Center, Bar-Ilan University, Ramat Gan, 52900, Israel.
Beitner
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002045:Bupivacaine / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005635:Fructosediphosphates / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology / Q000627:therapeutic use; D008546:Melanoma, Experimental / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000779:Anesthetics, Local; D000970:Antineoplastic Agents; D005635:Fructosediphosphates; D019298:Glucose-6-Phosphate; D000255:Adenosine Triphosphate; D008012:Lidocaine; C016473:glucose-1,6-bisphosphate; C029063:fructose-1,6-diphosphate; D002045:Bupivacaine