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Journal of B.U.ON. : official journal of the Balkan Union of Oncology

Quercetin reverses tamoxifen resistance in breast cancer cells.


PMID 26214621

Abstract

To investigate the effect of quercetin on the reversal of tamoxifen resistance in breast cancer cells, and explore the underlying mechanism. We established a tamoxifen-resistant breast cancer cell line (MCF-7Ca/TAM-R), and exposed it to different concentrations of quercetin (experimental group 1: 10 μM, group 2: 25 μM, and group 3: 50μM). Each group was further subdivided into 2 subgroups: 1) simultaneous administration of quercetin and 4-hydroxytamoxifen (OHT); 2) sequential administration of quercetin (12-h induction) followed by OHT. No drug exposure and OHT alone were used as controls. We determined cell survival, apoptosis, and expression of ERα (estrogen receptor α) and Her-2 (human epidermal growth factor receptor 2). With increasing dosage of quercetin, significant decrease in proliferation and increase in apoptosis was observed. Low concentrations of quercetin (10 μM) had no effects. We found no significant difference between simultaneous and sequential mode of drug administration. Further, with increasing dosage of quercetin, we observed a gradual reduction in Her-2 expression and upregulation of ERα. Again, no difference in Her-2 and ERα protein levels between simultaneous and sequential drug administration was noticed. Proliferation inhibition and apoptosis in MCF-7Ca/TAM-R cells increase with increasing dosage of quercetin. This suggests that quercetin can reverse tamoxifen resistance in breast cancer cells. The underlying mechanism likely involves upregulation of ERα combined with downregulation of Her-2. However, this effect is independent of whether quercetin and tamoxifen are administered simultaneously or sequentially.