Clotrimazole Preferentially Inhibits Human Breast Cancer Cell Proliferation, Viability and Glycolysis
Open Access
- 8 February 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (2), e30462
- https://doi.org/10.1371/journal.pone.0030462
Abstract
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. 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 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. 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.Keywords
This publication has 54 references indexed in Scilit:
- The glucose-responsive transcription factor ChREBP contributes to glucose-dependent anabolic synthesis and cell proliferationProceedings of the National Academy of Sciences of the United States of America, 2009
- E3 ubiquitin ligase APC/C-Cdh1 accounts for the Warburg effect by linking glycolysis to cell proliferationProceedings of the National Academy of Sciences, 2009
- Role of KCNMA1gene in breast cancer invasion and metastasis to brainBMC Cancer, 2009
- Understanding the Warburg Effect: The Metabolic Requirements of Cell ProliferationScience, 2009
- Role of mitochondria-associated hexokinase II in cancer cell death induced by 3-bromopyruvateBiochimica et Biophysica Acta (BBA) - Bioenergetics, 2009
- The molecular determinants of de novo nucleotide biosynthesis in cancer cellsCurrent Opinion in Genetics & Development, 2009
- Cancer Cell Metabolism: Warburg and BeyondCell, 2008
- Hypoxia-Inducible Factor 1 and Dysregulated c-Myc Cooperatively Induce Vascular Endothelial Growth Factor and Metabolic Switches Hexokinase 2 and Pyruvate Dehydrogenase Kinase 1Molecular and Cellular Biology, 2007
- In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitroNature Protocols, 2007
- On the Origin of Cancer CellsScience, 1956