Clotrimazole Preferentially Inhibits Human Breast Cancer Cell Proliferation, Viability and Glycolysis

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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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

Influence of chloride contamination on carbonation of cement-based materials

An experimental investigation was conducted to understand the effect of the presence of chloride on the carbonation front. Microstructural analysis was conducted to verify the carbonation development in material previously contaminated by chlorides. Accelerated tests were combined to understand how the presence of chlorides influences carbonation front and how chloride test method influences in these results. The results indicate that the presence of chloride decreases the carbonation front in cementbased materials. This behaviour is related to the pore refinement and humidity retention caused by chloride. The impact on carbonation reduction occurs at different levels, according to the testing method used

Supervised Curricular Internship and the development of management skills: a perception of graduates, undergraduates, and professors

Abstract Objective: Analyze the perception of graduates, undergraduates and professors about the teaching-learning process of the Supervised Curricular Internship (SCI) of Nursing Undergraduate Courses and in light of the development of management competencies. Method: Qualitative study based on the Mayan content analysis from a questionnaire of objective and discursive questions that evaluated the perception of 87 undergraduates, 280 graduates, and 48 professors from two universities in the state of São Paulo. Results: Four thematic categories emerged from this process and the development of management skills, highlighting the fundamental role of the supervising nurse in SCI and the need for greater presence of professors. Regarding management skills, the subjects emphasized leadership, resource management and performance of bureaucratic functions as essential skills. Final considerations: SCI is an environment that favors learning the profession and developing managerial skills; however, better coordination is required between educational institutions and SCI practice sites