Curcumin for the Prevention of Epithelial-Mesenchymal Transition in Endoxifen-Treated MCF-7 Breast Cancer Cells

Document Type: Research Articles

Authors

1 Master program in Biomedical Sciences, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.

2 Doctoral program in Biomedical Sciences, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.

3 Department of Biochemistry and Molecular Biology, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.

4 Department 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 short
term studies. This study was aimed to investigate the potential of curcumin in the prevention of EMT activation in
MCF-7 cells induced by endoxifen. Methods: MCF-7 breast cancer cells were treated with Endoxifen 1000 nM+betaestradiol
1 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 mRNA
E-cadherin, vimentin, TGF-β expression, total reactive oxygen species (ROS) and observed for morphological changes
using confocal microscope and transmission electron microscope. Result: MCF-7 cell viability was increased in
endoxifen + β-estradiol group. Cell viability was significantly decreased in curcumin 17 μM, but not in curcumin
8.5 μM group. Analysis of EMT markers at week 8 indicates that there were increase in vimentin and TGF-β mRNA
expressions, while E-cadherin mRNA expressions and TGF-β1 protein concentrations were shown to decrease. The
results showed that administration of curcumin in all the dose administered were incapable improving the expressions
of 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 microscope
and TEM showed the presence of mesenchymal cells and adherens junction. Conclusion: endoxifen treatments for
eight weeks resulted in upregulation of EMT markers and changes in morphology of MCF-7 breast cancer cells. The
addition of curcumin did not prevent the activation of EMT.

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