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Daidzein Inhibits Non-small Cell Lung Cancer Growth by Pyroptosis
Fanfan Zeng1,2, Yu Zhang1,2, Ting Luo1,3
1Jiangxi Provincial Key Laboratory of Cell Precision Therapy, School of Basic Medical Sciences, Jiujiang University, Jiujiang, 332005, Jiangxi, China.
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:
Further analysis of key pyroptosis-related molecules, such as ASC, CASP1, GSDMD, and IL-1β, revealed differential expression in NSCLC versus 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 daidzein. These findings offer insights into the molecular mechanisms underlying the anti-NSCLC effects of daidzein and could offer dietary recommendations for managing NSCLC.
Insights
Daidzein, a soy isoflavone, inhibits non-small cell lung cancer (NSCLC) by triggering pyroptosis, a programmed cell death. Key proteins ASC, CASP1, and IL-1β are identified as crucial targets for daidzein
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide.
- Daidzein, a soy isoflavone, shows potential in inhibiting NSCLC cell proliferation and migration.
- The precise molecular mechanisms of daidzein's anti-NSCLC effects require further elucidation.
Purpose of the Study:
- To investigate the molecular mechanisms by which daidzein inhibits NSCLC growth.
- To identify key molecular targets and pathways modulated by daidzein in NSCLC.
- To explore the potential of daidzein as a dietary intervention for NSCLC management.
Main Methods:
- An NSCLC mouse model was established and treated with daidzein.
- Proteomic analysis (mass spectrometry) was performed on tumor tissues to identify differentially expressed proteins (DEPs).
- Gene enrichment analysis, RT-qPCR, and Western blot were used to validate key molecular targets and pathways, including pyroptosis-related molecules.
Main Results:
- Proteomic analysis identified 601 DEPs, significantly enriched in immune regulatory functions and the NOD-like receptor signaling pathway, which is linked to pyroptosis.
- Key pyroptosis-related molecules (ASC, CASP1, IL-1β) showed differential expression in NSCLC and were upregulated by daidzein treatment, correlating with favorable prognosis.
- Daidzein treatment elevated mRNA and protein levels of ASC, CASP1, and IL-1β, confirming their role in daidzein-induced pyroptosis in NSCLC.
Conclusions:
- Daidzein effectively inhibits NSCLC growth through the induction of pyroptosis.
- ASC, CASP1, and IL-1β were identified as critical molecular targets mediating daidzein's anti-NSCLC effects.
- These findings provide mechanistic insights into daidzein's action and suggest its potential as a dietary strategy for NSCLC.
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