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. 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. 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.

中文翻译：

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橙皮素减轻阿霉素诱导的4T1乳腺癌细胞迁移

橙皮黄酮Hesperetin（Hst）广泛分布于包括柠檬在内的柑橘类水果中。Hst已显示具有生物活性，可作为抗氧化剂，消炎药，抗过敏药，降血脂药，血管保护药和抗癌药。这项研究旨在确定Hst和化学治疗剂阿霉素（Dox）作为针对4T1小鼠转移性乳腺癌细胞的辅助化学治疗剂的潜在组合。MTT分析结果表明，Hst在4T1细胞中表现出细胞毒性作用，其与Dox的组合显示出基于CI值的协同作用。Hst和Dox的组合增加了G2 / M期细胞周期停滞和凋亡诱导。Hst和Dox的组合抑制了4T1细胞的迁移并降低了MMP-9表达。结论，这项研究的结果表明，Hst通过诱导G2 / M期细胞周期停滞和凋亡而具有作为针对4T1细胞的Dox联合化学疗法的潜力。更重要的是，Hst降低了Dox诱导的迁移并降低了MMP-9表达。