铁死亡是一种独特的细胞死亡类型，与铁升高、抗氧化功能抑制和脂质过氧化增加共存。最近的研究表明，癌细胞对具有铁死亡活性的化合物特别敏感。葫芦素 B (CuB) 是一种具有有效生物学特性的三萜类化合物。它已被证明可以诱导癌细胞凋亡并抑制癌细胞转移。然而，该化合物的潜在机制仍不完全清楚。在本研究中，我们研究了 CuB 在乳腺癌细胞中的铁死亡效应，并评估了其与铁死亡诱导剂erastin 组合的影响。在这方面，进行MTT测定来分析细胞活力。用相关试剂盒测定脂质过氧化、氧化应激和细胞抗氧化能力。通过蛋白质印迹分析铁死亡蛋白的表达。结果表明，CuB 和erastin 联合处理可显着激活MCF-7 和MDA-MB-231 乳腺癌细胞的铁死亡途径。更重要的是，联合治疗改变了铁相关蛋白 IREB2 和 FPN1 的表达。总之，这项研究首次证明了 CuB 在乳腺癌细胞中的铁死亡潜力，并揭示了其对铁调节蛋白表达的影响。版权所有 © 2023。由 Elsevier Ltd 出版。

Ferroptosis is a unique type of cell death which co-exists with elevated iron, suppressed antioxidative function and increased lipid peroxidation. Recent studies have shown that cancer cells are particularly susceptible to the compounds with ferroptotic activities. Cucurbitacin B (CuB) is a triterpenoid with potent biological properties. It has been demonstrated to induce apoptosis and inhibit metastasis in cancer cells. However, the underlying mechanism of the compound is still not fully understood. In the present study, we investigated the ferroptotic effect of CuB in breast cancer cells and evaluated the impact of its combination with erastin, a ferroptosis inducer. In this regard, MTT assay was performed to analyze cell viability. Lipid peroxidation, oxidative stress and the cellular antioxidant capacity were determined with relevant kits. The expression of ferroptotic proteins were analyzed by western blotting. The results indicated that the combined treatment of CuB and erastin activated the ferroptotic pathways significantly in MCF-7 and MDA-MB-231 breast cancer cells. More importantly, the combination treatment altered the expression of iron-related proteins IREB2 and FPN1. In conclusion, this study demonstrated the ferroptotic potential of CuB in breast cancer cells for the first time, and revealed its impact on the expression of iron-regulating proteins.Copyright © 2023. Published by Elsevier Ltd.