Li Feifei, Qi Qin, Qiao Yu, Huang Yan, Lu Yuan, Gu Kan, Liu Huirong, Gao Chunfang, Liu Sheng, Wu Huangan
Medical Laboratory, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China.
Hospital Management Office, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
Int J Mol Med. 2025 Jul;56(1). doi: 10.3892/ijmm.2025.5552. Epub 2025 May 16.
Triple‑negative breast cancer (TNBC) exhibits a high degree of malignancy and a propensity for metastasis, ultimately resulting in unfavorable patient outcomes. Valeton is a common herb used in traditional Chinese medicine to treat TNBC. Curcumenol (Cur) is a natural compound derived from Valeton, the effects of which on breast cancer remain under‑reported. The present study elucidated that Cur could effectively inhibit the survival ability of TNBC cells and enhance their sensitivity to paclitaxel. Western blotting (WB) further revealed that Cur modulated apoptosis and epithelial‑mesenchymal transition (EMT) in TNBC. Findings from animal experiments further validated these observations. In the established TNBC mouse model, Cur was shown to exert an inhibitory effect on tumor growth, effectively attenuate EMT and substantially reduce the incidence of lung metastasis. Integrated analyses using RNA sequencing, WB and reverse transcription‑quantitative polymerase chain reaction demonstrated that Cur markedly downregulated the expression levels of solute carrier family 7 member 11 (SLC7A11), phosphorylated‑NF‑κB and TGF‑β. Molecular docking studies further validated that Cur can establish stable interactions with SLC7A11. In‑depth bioinformatics analysis revealed a positive association between high SLC7A11 expression and reduced disease‑free survival in patients with breast cancer. Additionally, in TNBC cells, Cur was revealed to reduce the mitochondrial membrane potential and promote the accumulation of lipid reactive oxygen species. Subsequent experimental investigations demonstrated that Cur can counteract the inhibitory influence of ferrostatin‑1 on ferroptosis. These findings strongly implied a potential underlying mechanism, suggesting that Cur may impede the malignant progression of TNBC via the modulation of ferroptosis. In conclusion, the findings of the present study underscore the marked efficacy of Cur in hampering the progression of TNBC by suppressing the SLC7A11/NF‑κB/TGF‑β signaling pathway.
三阴性乳腺癌（TNBC）具有高度恶性和转移倾向，最终导致患者预后不良。莪术是一种常用于治疗TNBC的传统中药。莪术醇（Cur）是从莪术中提取的天然化合物，其对乳腺癌的影响报道较少。本研究阐明，Cur可有效抑制TNBC细胞的生存能力，并增强其对紫杉醇的敏感性。蛋白质免疫印迹法（WB）进一步显示，Cur可调节TNBC中的细胞凋亡和上皮-间质转化（EMT）。动物实验结果进一步验证了这些观察结果。在建立的TNBC小鼠模型中，Cur对肿瘤生长具有抑制作用，可有效减弱EMT并显著降低肺转移发生率。使用RNA测序、WB和逆转录-定量聚合酶链反应进行的综合分析表明，Cur显著下调溶质载体家族7成员11（SLC7A11）、磷酸化-NF-κB和TGF-β的表达水平。分子对接研究进一步验证了Cur可与SLC7A11建立稳定的相互作用。深入的生物信息学分析揭示，SLC7A11高表达与乳腺癌患者无病生存期缩短呈正相关。此外，在TNBC细胞中，Cur可降低线粒体膜电位并促进脂质活性氧的积累。随后的实验研究表明，Cur可抵消铁死亡抑制因子1对铁死亡的抑制作用。这些发现强烈暗示了一种潜在的机制，表明Cur可能通过调节铁死亡来阻碍TNBC的恶性进展。总之，本研究结果强调了Cur通过抑制SLC7A11/NF-κB/TGF-β信号通路来阻碍TNBC进展的显著疗效。
