Enhancement of doxorubicin efficacy by diosmetin through DNA damage accumulation and P-glycoprotein inhibition in breast cancer cells

Abstract

Abstract Doxorubicin (DOX) is widely used in treatment; however, its efficacy is often compromised by multidrug resistance (MDR), limiting therapeutic outcomes. This study investigates the anticancer potential of diosmetin (DT), a metabolite of diosmin commonly used in chronic venous insufficiency, and its ability to enhance the efficacy of DOX in the treatment of breast cancer. Several breast cancer cell lines were used to assess the effects of DT and DOX on cell viability. The MCF-7 cell line, which showed the most significant effect, was selected for further investigation. The effects of DT on apoptosis, DNA damage, and P-glycoprotein expression and activity were analyzed. DT significantly enhanced DOX-induced apoptosis and DNA damage, while downregulating ABCB1 expression and activity, a key factor in MDR development. These findings highlight the potential of DT as a valuable adjuvant in breast cancer therapy by enhancing the efficacy of DOX. Its ability to overcome multidrug resistance mechanisms underlines its potential for future clinical trials aimed at developing effective treatments.