Targeting multiple proliferation pathways as a novel breast cancer treatment

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Talia Hatkevich (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Yashomati Patel

Abstract: Estrogen receptor alpha positive (ERa+) breast cancer cells proliferate and survive by utilizing multiple pathways. Thus, combination chemotherapies targeting multiple pathways may be used to decrease ERa+ breast cancer cell density. Tamoxifen (Tam), an estrogen antagonist, has been used for over 30 years to inhibit ERa+ breast cancer proliferation. Naringenin (Nar), a flavonoid, has been shown to reduce the proliferation of ERa+ breast cancer cells by inhibiting extracellular signal-regulated kinases 1/2 (ERK 1/2) and AKT. In our studies, we investigated the effects of a combination of Tam and Nar on MCF-7 ERa+ breast cancer cells. We showed that Tam and Nar significantly inhibited cellular proliferation and viability by flow cytometry analysis when compared to Tam alone. Proliferation was inhibited by the reduction of expression of AKT and ERK 1/2, as determined by immunoblot analysis. We have investigated the combination of Nar and Tam on Tam resistant (Tam-R) cells. Our results demonstrate that Nar alone impaired cellular proliferation and viability in Tam-R cells. In the absence of lipophilic compounds, Nar eliminated the phosphorylation of ERK 1/2, as determined by immunoblot analysis. Taken together, our results suggest that a combination treatment of Nar and Tam is more effective in inhibiting cellular proliferation and viability than Tam alone in ERa+ breast cancer cells. This combination treatment has the potential to improve the efficacy of breast cancer chemotherapy regimens.

Additional Information

Language: English
Date: 2013
AKT, ERK 1/2, Naringenin, Tamoxifen
Tamoxifen $x Therapeutic use
Flavonoids $x Therapeutic use
Breast $x Cancer $x Treatment

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