BackgroundClotrimazole 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.Methodology/Principal FindingsThree 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 Ki 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/SignificanceClotrimazole 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.
This work aims to synthesize combustion reaction, functionalized with chitosan nanoparticles and characterize ZnAl1.94(Yb:Er)0.06O4, codoped with x = 0.06 mol in the proportion 5:1 of Yb:Er. Nanoparticles before and after functionalization were characterized by XRD, TGA/DTA, FTIR and SEM. The results show that before and after functionalization presented ZnAl2O4majority phase and Al2Yb4O as secondary phase. Multiple bands around 1100 cm-1and 1040 cm-1corresponding to the asymmetric stretching Si-O confirms the functionalization of nanoparticles. Nanoparticles presented before functionalization morphology heterogeneous, consisting of clusters of particles with near-spherical shape, large particle size distribution, consisting of large clusters with size around 3 µm and smaller clusters in the shape of plates with size in order of 0.5 µm. After functionalization, the morphology shows the formation of a film consisting of amorphous phase and crystalline phase. The mass loss for the nanoparticles before and after functionalization was 7.2 and 39%, respectively.
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