Daidzein Inhibits Non-small Cell Lung Cancer Growth by Pyroptosis

作者：Fanfan Zeng, Yu Zhang, Ting Luo, Chengman Wang, Denggang Fu, Xin Wang · 发表于：Current Pharmaceutical Design · 年份：2024 · DOI：10.2174/0113816128330530240918073721 · 被引用次数：8 · 研究领域：Phytoestrogen effects and research、Inflammasome and immune disorders、Tryptophan and brain disorders

INTRODUCTION: Non-small cell lung cancer (NSCLC) represents the leading cause of cancer deaths in the world. We previously found that daidzein, one of the key bioactivators in soy isoflavone, can inhibit NSCLC cell proliferation and migration, while the molecular mechanisms of daidzein in NSCLC remain unclear. METHODS: We developed an NSCLC nude mouse model using H1299 cells and treated the mice with daidzein (30 mg/kg/day). Mass spectrometry analysis of tumor tissues from daidzein-treated mice identified 601 differentially expressed proteins (DEPs) compared to the vehicle-treated group. Gene enrichment analysis revealed that these DEPs were primarily associated with immune regulatory functions, including B cell receptor and chemokine pathways, as well as natural killer cell-mediated cytotoxicity. Notably, the NOD-like receptor signaling pathway, which is closely linked to pyroptosis, was significantly enriched. RESULTS: normal tissues. High levels of ASC and CASP1 were associated with a favorable prognosis in NSCLC, suggesting that they may be critical effectors of daidzein's action. In NSCLC-bearing mice treated with daidzein, RT-qPCR and Western blot analyses showed elevated mRNA and protein levels of ASC, CASP1, and IL-1β but not GSDMD, which was consistent with the proteomic data. CONCLUSION: In summary, this study demonstrated that daidzein inhibits NSCLC growth by inducing pyroptosis. Key pathway modulators ASC, CASP1, and IL-1β were identified as primary targets of da...