Clotrimazole decreases glycolysis and the viability of lung carcinoma and colon adenocarcinoma cells.
Glycolysis is known to be the primary energy source in most cancer cells. We investigated here the effect of clotrimazole (1-(alpha-2-chlorotrityl)imidazole), the antifungal azole derivative, which was recently recognized as calmodulin antagonist, on the levels of glucose 1,6-bisphosphate and fructose 1,6-bisphosphate, the two stimulatory signal molecules of glycolysis, and on ATP content and cell viability in LL/2 Lewis lung carcinoma cells and CT-26 colon adenocarcinoma cells. We found that clotrimazole induced a significant, dose- and time-dependent reduction in the levels of glucose 1,6-bisphosphate, fructose 1,6-bisphosphate, ATP, and cell viability. These findings suggest that clotrimazole causes a reduction in glycolysis and ATP levels, which eventually leads to cell destruction after 3 h of treatment. Since cell proliferation was also reported to be inhibited by calmodulin antagonists, this substance is most promising agent in treatment of cancer by inhibiting both cell proliferation and the glycolytic supply of ATP required for cancer cell growth.
Penso
Julia
J
Health Sciences Research Center, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
Beitner
Rivka
R
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002470:Cell Survival / Q000187:drug effects*; D003022:Clotrimazole / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D005635:Fructosediphosphates / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D014407:Tumor Cells, Cultured
D002147:Calmodulin; D005635:Fructosediphosphates; D019298:Glucose-6-Phosphate; D000255:Adenosine Triphosphate; C016473:glucose-1,6-bisphosphate; D003022:Clotrimazole; C029063:fructose-1,6-diphosphate