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Curcumin for the Prevention of Epithelial-Mesenchymal Transition in Endoxifen-Treated MCF-7 Breast Cancer Cells
Authors:P Paramita1Bantari WK Wardhani2Septelia Inawati Wanandi3Melva Louisa4
Affiliation:1Master program in Biomedical Sciences, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.2Doctoral program in Biomedical Sciences, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.3Department of Biochemistry and Molecular Biology, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.4Department of Pharmacology and Therapeutics, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
Abstract:Background: Curcumin was shown to reduce epithelial-mesenchymal transition (EMT) markers in previous shortterm studies. This study was aimed to investigate the potential of curcumin in the prevention of EMT activation inMCF-7 cells induced by endoxifen. Methods: MCF-7 breast cancer cells were treated with Endoxifen 1000 nM+betaestradiol1 nM with or without curcumin (8.5μM or 17 μM). Cells treated with dimethyl sulfoxide (DMSO) 0.001%were used as negative control. After 8 weeks of continuous treatment, the cells were counted, analyzed for mRNAE-cadherin, vimentin, TGF-β expression, total reactive oxygen species (ROS) and observed for morphological changesusing confocal microscope and transmission electron microscope. Result: MCF-7 cell viability was increased inendoxifen + β-estradiol group. Cell viability was significantly decreased in curcumin 17 μM, but not in curcumin8.5 μM group. Analysis of EMT markers at week 8 indicates that there were increase in vimentin and TGF-β mRNAexpressions, while E-cadherin mRNA expressions and TGF-β1 protein concentrations were shown to decrease. Theresults showed that administration of curcumin in all the dose administered were incapable improving the expressionsof vimentin, TGF-β1 and E-cadherin. There was a decrease in ROS concentration in curcumin treated cells (8.5 μM)while in curcumin 17 μM, ROS concentration was increased. Morphological observation using confocal microscopeand TEM showed the presence of mesenchymal cells and adherens junction. Conclusion: endoxifen treatments foreight weeks resulted in upregulation of EMT markers and changes in morphology of MCF-7 breast cancer cells. Theaddition of curcumin did not prevent the activation of EMT.
Keywords:curcumin  endoxifen  epithelial-mesenchymal transition (EMT)  Vimentin  TGF-β1
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