| Summary: | Abstract Background Hesperetin (Hst), a citrus flavanone, is widely distributed among citrus fruits, including lemons. Hst has been shown to possess bioactivity as an antioxidant, anti-inflammatory, anti-allergic, hypolipidemic, vasoprotector, and anticancer agent. This study aimed to identify potential combinations of Hst and the chemotherapeutic agent doxorubicin (Dox) as co-chemotherapy agents against 4T1 murine metastatic breast cancer cells. Results MTT assay results showed that Hst exhibited cytotoxic effect in 4T1 cells, and its combination with Dox showed a synergistic effect based on the CI value. The combination of Hst and Dox increased G2/M phase cell cycle arrest and apoptosis induction. The combination of Hst and Dox inhibited migration and decreased MMP-9 expression in 4T1 cells. Conclusion In conclusion, the results of this study show that Hst has potential as a Dox co-chemotherapy against 4T1 cells by inducing G2/M phase cell cycle arrest and apoptosis. More importantly, Hst reduces Dox-induced migration and decreases MMP-9 expression.
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