Abstract
The multidrug resistance phenotype is one of the major problems in development of cancer cell resistance to chemotherapy. Some natural compounds from medicinal plants have demonstrated promising capacity in enhancing anticancer effects in drug resistant cancer cells. We aimed to investigate whether mangiferin might have an ability to re-sensitize MCF-7 breast cancer cells previously treated with short-term doxorubicin in vitro, through the modulation of efflux transporters, P-glycoprotein (P-gp), MRP1 and BCRP. We exposed MCF-7 breast cancer cells pretreated with doxorubicin for 10 days to mangiferin (10, 25 or 50 μM) for 96 hours. Afterwards, we evaluated influence on cell viability and level of mRNA expression of P-gp, MRP1 and BCRP. Doxorubicin given in combination with mangiferin at low concentrations (10 and 25 μM) failed to give significant reduction in cell viability, while at the highest concentrations, the combination significantly reduced cell viability. The mRNA expression analysis of P-gp, MRP1 and BCRP showed that mangiferin had inhibitory effects on P-gp but no effects on MRP1 and BCRP. In conclusion, we suggest that mangiferin at high concentrations can be used as chemosensitizer for doxorubicin therapy. This effect might be attributed by inhibitory effects of mangiferin on P-glycoprotein expression.
Highlights
Doxorubicin is an effective chemotherapeutic agents, which has been used extensively for treatment in various cancer, including breast cancer (Smith et al, 2006; Ghebeh et al, 2010; Andreopoulou and Sparano, 2013)
We aimed to investigate whether mangiferin might have an ability to re-sensitize MCF-7 breast cancer cells previously treated with short-term doxorubicin in vitro, through the modulation of efflux transporters, P-glycoprotein (P-gp), multidrug resistance associated protein-1 (MRP1) and BCRP
In this study we aim to investigate whether mangiferin have the ability to re-sensitize breast cancer cells previously treated with short-term doxorubicin in vitro, through the modulation of efflux transporters, P-gp, MRP1 and BCRP
Summary
Doxorubicin is an effective chemotherapeutic agents, which has been used extensively for treatment in various cancer, including breast cancer (Smith et al, 2006; Ghebeh et al, 2010; Andreopoulou and Sparano, 2013). The incidence of cancer cell resistance to doxorubicin is quite common, which leads to unsuccessful treatments in many patients (Smith et al, 2006). The most common MDR is due to the increased efflux pumps in the cell membrane including P-glycoprotein, multidrug resistance associated protein-1 (MRP1) and breast cancer resistance protein (Choi, 2005). Doxorubicin was known as substrate as well as inducers of the major efflux transporters in breast cancer cells, P-glycoprotein, MRP1 and BCRP (Chien and Moasser, 2008; Choi, 2005)
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