Background: Clotrimazole is an azole derivative with promising anti-cancer effects. This drug interferes with the activity of\nglycolytic enzymes altering their cellular distribution and inhibiting their activities. The aim of the present study was to\nanalyze the effects of clotrimazole on the growth pattern of breast cancer cells correlating with their metabolic profiles.\nMethodology/Principal Findings: Three cell lines derived from human breast tissue (MCF10A, MCF-7 and MDA-MB-231)\nthat present increasingly aggressive profiles were used. Clotrimazole induces a dose-dependent decrease in glucose uptake\nin all three cell lines, with Ki values of 114.3611.7, 77.167.8 and 37.864.2 mM for MCF10A, MCF-7 and MDA-MB-231,\nrespectively. Furthermore, the drug also decreases intracellular ATP content and inhibits the major glycolytic enzymes,\nhexokinase, phosphofructokinase-1 and pyruvate kinase, especially in the highly metastatic cell line, MDA-MB-231. In this\nlast cell lineage, clotrimazole attenuates the robust migratory response, an effect that is progressively attenuated in MCF-7\nand MCF10A, respectively. Moreover, clotrimazole reduces the viability of breast cancer cells, which is more pronounced on\nMDA-MB-231.\nConclusions/Significance: Clotrimazole presents deleterious effects on two human breast cancer cell lines metabolism,\ngrowth and migration, where the most aggressive cell line is more affected by the drug. Moreover, clotrimazole presents\nlittle or no effect on a non-tumor human breast cell line. These results suggest, at least for these three cell lines studied, that\nthe more aggressive the cell is the more effective clotrimazole is.
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