Curcumenol inhibits malignant progression and promotes ferroptosis via the SLC7A11/NF‑κB/TGF‑β pathway in triple‑negative breast cancer.

Abstract

Triple‑negative breast cancer (TNBC) exhibits a high degree of malignancy and a propensity for metastasis, ultimately resulting in unfavorable patient outcomes. Curcuma phaeocaulis Valeton is a common herb used in traditional Chinese medicine to treat TNBC. Curcumenol (Cur) is a natural compound derived from C. phaeocaulis 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.