Abstract
Objective: The aim of the present study was to determine whether curcumin (CM) can prevent drug sensitivity of breast cancer (BC) cells when E andβ-E2 are administered together and whether the underlying mechanism involves modulation of drug efflux transporters.Methods: MCF7 BC cells were treated with the vehicle only, E+β-E2, or E+β-E2+CM repeatedly for 8 weeks. Afterward, the cells were harvested,counted, and isolated for total RNA extraction. Total RNA was then processed into cDNA and further processed for the determination of mRNAexpression patterns of drug efflux transporters (P-glycoprotein, BCRP, and MRP1).Results: Decreased sensitivity of BC cells was shown by the increased cell viability of MCF7 cells after 8 weeks. This condition was accompanied withincreased mRNA expression of P-glycoprotein, BCRP, and MRP1 in cells treated with E+β-E2, as compared with the vehicle only. CM, administered incombination with E+β-E2, resulted in decreased cell viability versus E and β-E2 and also decreased in mRNA expression of P-glycoprotein, BCRP, andMRP1.Conclusion: CM partially reversed the sensitivity loss of BC cells to E in the presence of β-E2 by modulating drug efflux transporters.
Highlights
Breast cancer (BC) is the most common type of cancer in women
After 8 weeks of treatment with E and β-E2, the efficacy of E was clearly lost, as BC cell viability had surpassed that of the control cells
Concomitant treatment with a low concentration of CM did not improve the sensitivity of BC cells to E, whereas larger concentrations showed good suppression of cell viability after 8 weeks of treatment (Fig. 1)
Summary
Treatments for BC include surgery, radiation therapy, endocrine therapy, and chemotherapy. Tamoxifen (TMX) is the most common estrogen receptor (ER) modulator prescribed for ER-positive BC [1]. TMX is metabolized by CYP3A4 and CYP2D6 into several metabolites, which include 4-hydroxy-TMX, N-desmethyl-TMX, and 4-hydroxyN-desmethyl-TMX, which is known as endoxifen (E) [2]. E is an active metabolite of TMX that has recently been developed as a new endocrine therapeutic agent for BC patients unresponsive to antiestrogen treatment [3]. E exerts its anticancer effects by degrading ER alpha, which leads to the inhibition of estrogen-induced BC cell proliferation [4]. BC cell resistance to endocrine treatment, including E, is likely to develop overtime [5,6,7]
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