硫氧还蛋白还原酶（TrxR）的异常激活与肿瘤的发生和进展相关，表明TrxR抑制剂可以用作抗肿瘤药物。在本研究中，我们评估了 eupalinilides B 对结直肠癌细胞的抗癌功效。 Eupalinilides B 主要靶向 TrxR 中保守的硒代半胱氨酸 498 残基。此外，它以不可逆的方式抑制酶活性。 eupalinilides B在药理上抑制TrxR后，活性氧积累，细胞内氧化还原平衡被打破，最终引起氧化应激诱导肿瘤细胞凋亡。值得注意的是，eupalinilides B 治疗可抑制体内肿瘤生长。 eupalinilides B 靶向 TrxR 揭示了 eupalinilides B 的新机制，并为开发 eupalinilides B 作为治疗癌症的候选抗肿瘤化疗药物提供了见解。版权所有 © 2024。由 Elsevier B.V. 出版。

Aberrant activation of thioredoxin reductase (TrxR) is correlated with tumor occurrence and progression, suggesting that TrxR inhibitors can be used as antitumor agents. In this study, we evaluated the anticancer efficacy of eupalinilides B on colorectal cancer cells. Eupalinilides B primarily targeted the conserved selenocysteine 498 residues in TrxR. Besides, it inhibited the enzyme activity in an irreversible manner. After eupalinilides B was used to pharmacologically inhibit TrxR, reactive oxygen species accumulated, and the intracellular redox balance was broken, finally causing oxidative stress-induced tumor cell apoptosis. Significantly, eupalinilides B treatment inhibited in vivo tumor growth. Targeting TrxR by eupalinilides B reveals the new mechanism underlying eupalinilides B and provides insight in developing eupalinilides B as the candidate antitumor chemotherapeutic agent for the treatment of cancer.Copyright © 2024. Published by Elsevier B.V.