Combinatorial Effects of Chrysin with Doxorubicin, 5-Fluorouracil, and Cyclophosphamide on Triple-Negative Breast Cancer Cell Line.

Background: The primary challenges associated with chemotherapy treatment include the development of drug resistance. Chrysin (CH) has the potential to enhance the therapeutic efficacy of conventional chemotherapeutic agents. Additionally, CH, with its antioxidant properties, can reduce the side effects caused by reactive oxygen species (ROS) from chemotherapy. Objectives: This study focused on investigating the combination impact of CH with either 5-fluorouracil (5-FU), doxorubicin (DOX), or cyclophosphamide (CP) on the triple-negative breast cancer (TNBC) MDA-MB-231 cell line. Methods: Cytotoxicity was investigated using the MTT assay. The checkerboard microplate method was utilized to determine the effects of drug interactions. Apoptosis and cell cycle distribution were measured by flow cytometry. The classical scratch assay was used to examine cell migration ability. Results: The combination of 5-FU and DOX showed synergistic effects with CH (FIX < 1). Conversely, the interaction between CH and CP resulted in non-additive effects (FIX > 1). The combination treatment of CH with a chemotherapeutic drug was more effective in inducing early apoptosis than the drug alone and the control (P < 0.05). An increase in the sub-G1 phase was observed upon treatment with the combination of CH and chemotherapeutic drugs compared with the control and drugs alone (P < 0.05). Co-administration of CH with chemotherapeutic drugs induced a significant decrease in cell migration compared with the control and chemotherapeutic drugs alone (P < 0.05). Conclusions: The results revealed that combination therapy involving CH in conjunction with 5-FU and DOX demonstrated a more substantial therapeutic effect on TNBC cells than treatments with 5-FU and DOX individually.