Rhoifolin potentiates the anti-cancer activity of doxorubicin in MDA-MB-231 triple-negative breast cancer cells

Background : The combination of chemotherapeutic agents with natural compounds has gained attention as a strategy to improve treatment effectiveness and reduce adverse effects of cancer therapies. This study investigates the potential use of rhoifolin, a citrus-derived flavonoid, to sensitize triple-negative breast cancer cells (MDA-MB-231) to doxorubicin. Materials and methods : The cytotoxicity of rhoifolin, doxorubicin, and their combination was assessed via MTT assay. Cell migration and proliferation were evaluated through scratch and colony formation assays, respectively. Caspase 3, Bax, and Bcl-2 gene expression were analyzed to explore apoptotic mechanisms. Results : The IC 50 values were 6.22 µM for doxorubicin and 102 µM for rhoifolin. Rhoifolin significantly enhanced doxorubicin’s cytotoxic effect with a combination index <1 at various ratios. At a dose of 50 µM rhoifolin, the anti-migratory effect of 1.5 µM doxorubicin was significantly increased (p < 0.01). The combination reduced colony formation to 72.5 ± 8.5 colonies compared to 202 ± 9 in the control group. Moreover, the combination increased caspase 3 gene expression by 22.2-fold. Conclusion : Rhoifolin potentiated the anti-cancer effects of doxorubicin, suggesting its potential as an adjuvant therapy in cancer.