title: Clotrimazole preferentially inhibits human breast cancer cell proliferation, viability and glycolysis.
abstract: BACKGROUND
  Clotrimazole is an azole derivative with promising anti-cancer effects. This drug interferes with the activity of glycolytic enzymes altering their cellular distribution and inhibiting their activities. The aim of the present study was to analyze the effects of clotrimazole on the growth pattern of breast cancer cells correlating with their metabolic profiles.
  
  
  RESULTS
  Three cell lines derived from human breast tissue (MCF10A, MCF-7 and MDA-MB-231) that present increasingly aggressive profiles were used. Clotrimazole induces a dose-dependent decrease in glucose uptake in all three cell lines, with K(i) values of 114.3±11.7, 77.1±7.8 and 37.8±4.2 µM for MCF10A, MCF-7 and MDA-MB-231, respectively. Furthermore, the drug also decreases intracellular ATP content and inhibits the major glycolytic enzymes, hexokinase, phosphofructokinase-1 and pyruvate kinase, especially in the highly metastatic cell line, MDA-MB-231. In this last cell lineage, clotrimazole attenuates the robust migratory response, an effect that is progressively attenuated in MCF-7 and MCF10A, respectively. Moreover, clotrimazole reduces the viability of breast cancer cells, which is more pronounced on MDA-MB-231.
  
  
  CONCLUSIONS
  Clotrimazole presents deleterious effects on two human breast cancer cell lines metabolism, growth and migration, where the most aggressive cell line is more affected by the drug. Moreover, clotrimazole presents little or no effect on a non-tumor human breast cell line. These results suggest, at least for these three cell lines studied, that the more aggressive the cell is the more effective clotrimazole is.
authors.affiliation: Laboratório de Oncobiologia Molecular, Departamento de Fármacos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Cristiane M
authors.initials: CM
authors.lastname: Furtado
authors.forename: Mariah C
authors.initials: MC
authors.lastname: Marcondes
authors.forename: Mauro
authors.initials: M
authors.lastname: Sola-Penna
authors.forename: Maisa L S
authors.initials: ML
authors.lastname: de Souza
authors.forename: Patricia
authors.initials: P
authors.lastname: Zancan
mesh_terms: D000970:Antineoplastic Agents; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003022:Clotrimazole / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D055442:Metabolome
chemical_list: D000970:Antineoplastic Agents; D003022:Clotrimazole