Silymarin increases the sensitivity of breast cancer cells to doxorubicin in doxorubicin-induced MCF-7 cells by inhibiting breast cancer resistance protein expression

Abstract

The efflux transporter breast cancer resistance protein (BCRP) is typically overexpressed in cancer cells with reduced doxorubicin sensitivity. Silymarin is known to exert inhibitory effects against BCRP; therefore, the exposure of doxorubicin-resistant breast cancer cells to silymarin is expected to increase their sensitivity to doxorubicin. Here, we examined the effect of silymarin addition on the sensitivity of breast cancer cells to doxorubicin. MCF-7 breast cancer cells were exposed to doxorubicin for 14 days. Subsequently, the cells were treated with different concentrations of silymarin (10, 25, 50, or 100 μM) with or without doxorubicin. On days 3 and 7 following the treatment, cells were analyzed for viability and BCRP mRNA expression. MCF-7 cells exposed to doxorubicin for 14 days showed reduced sensitivity to doxorubicin, as indicated by the 9.5-fold shift in cytotoxicity concentration and the 9.7-fold increase in BCRP mRNA expression. Treatment with the combination of different concentrations of silymarin and doxorubicin significantly decreased the percent cell viability and reduced BCRP mRNA expression on days 3 and 7. The combination of doxorubicin and silymarin increased the sensitivity of MCF-7 cells to doxorubicin through the inhibition of BCRP mRNA expressions by silymarin.