放射抗性给癌症治疗带来了重大障碍。莲子荚提取物 (LSE) 对多种癌细胞具有抗癌作用。然而，其对抗放射抗性肿瘤的潜力仍不清楚。在本研究中，我们旨在研究LSE对放射抗性乳腺癌细胞的影响，探索其潜在机制，并确定其细胞毒性作用的主要成分。使用 70% 乙醇提取的 LSE 与亲本细胞相比，对放射抗性乳腺癌细胞表现出选择性细胞毒性作用。化学分析确定槲皮素及其衍生物、金丝桃苷和密奎连苷是造成这些选择性作用的主要成分。值得注意的是，与金丝桃苷和密克丽宁相比，槲皮素对放射抗性乳腺癌细胞表现出最有效的细胞毒性。进一步的研究表明，这些化合物抑制DNA修复系统的激活，导致DNA损伤的积累并诱导细胞凋亡。重要的是，它们有效地抑制了 ACSL4 的表达，ACSL4 是先前与放射抗性相关的一个因素。在一项体内研究中，槲皮素表现出对辐射抗性荷瘤小鼠肿瘤生长的显着抑制作用。总而言之，我们的研究结果强调了 LSE 及其主要成分槲皮素及其衍生物在克服乳腺癌放射抗性方面的潜力。这项研究提供了令人信服的证据，支持使用 LSE 作为未来辅助治疗的药物来源，以对抗乳腺癌的放射抗性。© 2024 国际生物化学和分子生物学联盟。

Radioresistance poses a significant obstacle in cancer treatment. Lotus seedpod extract (LSE) has demonstrated anticancer effects in various cancer cells. However, its potential against radioresistant tumors remains unclear. In this study, we aimed to investigate the effect of LSE on radioresistant breast cancer cells, explore the underlying mechanism, and identify the major constituents responsible for its cytotoxic effect. LSE, extracted using 70% ethanol, exhibited selective cytotoxic effects against radioresistant breast cancer cells compared with their parental cells. Chemical analysis identified quercetin and its derivatives, hyperoside and miquelianin, as the major constituents responsible for these selective effects. Notably, quercetin displayed the most potent cytotoxicity against radioresistant breast cancer cells compared with hyperoside and miquelianin. Further investigation revealed that these compounds inhibited the activation of DNA repair systems, leading to the accumulation of DNA damage and the induction of apoptosis. Importantly, they efficiently suppressed the expression of ACSL4, a factor previously associated with radioresistance. In an in vivo study, quercetin exhibited a significant suppression of tumor growth in radioresistant tumor-bearing mice. Taken together, our findings highlight the potential of LSE and its major constituents, quercetin and its derivatives, in overcoming radioresistance in breast cancer. This study provides compelling evidence to support the use of LSE as a medicinal source for the future adjunctive therapy to combat radioresistance in breast cancers.© 2024 International Union of Biochemistry and Molecular Biology.