A potential role for naringenin in reversing tamoxifen resistance in MCF-7 breast cancer cells

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Joseph Ramos (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Yashomati Patel

Abstract: Tamoxifen has been used as an effective treatment against breast cancer for over 30 years. However, tamoxifen resistance has become a major hurdle to effective treatment. Previous studies have implicated up-regulation of the PI3K and MAPK pathways as being involved in the growth exhibited by tamoxifen resistant cells. Data from our lab and others have shown naringenin to have the ability to impair both of these signaling pathways. For this study, I investigated whether naringenin, a flavanone, could reverse the proliferation observed in tamoxifen-resistant cells (TAM-R). MCF-7 cells were exposed to low levels of 4-OH-tamoxifen (1 µM) for 10 months in order to generate a tamoxifen-resistant cell line, TAM-R. These cells were then cultured under various combinations of treatment with tamoxifen and naringenin. TAM-R cells demonstrated a clear ability to proliferate in the presence of tamoxifen as measured using cell counting and an MTT assay. However, the addition of naringenin reversed that proliferation. The TAM-R cells also exhibited an up-regulation of the MAPK pathway which was also reversed by treatment with naringenin as measured by western blot analysis. In addition, treatment with tamoxifen and naringenin together led to a greater reduction in cell growth than either treatment alone. Confocal microscopy was also employed to look for any changes in the localization patterns of the estrogen receptor alpha (ERα). ERα was found predominantly in the nucleus in MCF-7 cells. Upon treatment with tamoxifen, this pattern changed to a peri-nuclear localization. Once the cells attained tamoxifen resistance, the ERα displayed an even pattern across the cell. However, upon treatment of the TAM-R cells with naringenin, the ERα localization returned to a peri-nuclear pattern similar to that seen in the tamoxifen-sensitive cells. The results from this study clearly demonstrate the ability of naringenin to reverse the proliferation normally seen in TAM-R cells. Naringenin also appears to have a synergistic effect with tamoxifen on growth impairment. There is also evidence these changes are taking place through the MAPK pathway. Taken together, these results open up the possibility of treatment with naringenin as a means to combat tamoxifen resistance.

Additional Information

Language: English
Date: 2012
Erk, Estrogen Receptor, MCF-7, Naringenin, Resistance, Tamoxifen
Drug resistance in cancer cells
Breast $x Cancer $x Treatment

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