Sanguinarine Induces Pyroptosis via the Hippo Signaling Pathway and Remodels the Tumor Immune Microenvironment in Lung Adenocarcinoma.
7 affiliations
- 1Department of Oncology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
- 2Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Shanghai Pudong Hospital, Fudan University, Shanghai 200032, China.
- 3Fudan University Shanghai Cancer Center, Shanghai 200032, China.
- 4Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
- 5Bayinguoleng Mongolian Autonomous Prefecture Hygiene School, Xinjiang Province 841000, China.
- 6Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
- 7Institute of Respiratory Diseases, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Abstract
Sanguinarine (SAN), a natural alkaloid derived from Papaveraceae plants, is an active component in traditional Chinese medicines. SAN exerts inhibitory effects on tumor cells, but research on its effects on lung adenocarcinoma (LUAD) and the underlying mechanisms remains limited. The Hippo signaling pathway is commonly downregulated in LUAD, making it a key target for therapeutic intervention. Our study reveals that SAN significantly inhibits LUAD. Mechanistically, SAN bound to Large Tumor Suppressor 1 (LATS1) and promoted its phosphorylation, thereby activating the Hippo pathway and pyroptosis in LUAD. Notably, YAP overexpression inhibited pyroptosis and weakened the antitumor effect of SAN, further confirming that SAN exerts its antitumor effects by regulating the Hippo-YAP axis. Findings from both in vivo experiments and single-cell RNA sequencing consistently show that SAN remodels the tumor immune microenvironment and inhibits tumor growth. Specifically, we observed significant changes in the tumor microenvironment, including increased CD8⁺ T cell infiltration and a notably reduced number of myofibroblastic cancer-associated fibroblasts. Collectively, our findings establish SAN as a candidate therapeutic agent that exerts antitumor effects through dual modulation of the Hippo-mediated pyroptosis pathway and tumor immunity, providing a mechanistic basis for its potential clinical application in LUAD.
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BibTeX
@article{yang2026sanguinarine,
title = {{Sanguinarine Induces Pyroptosis via the Hippo Signaling Pathway and Remodels the Tumor Immune Microenvironment in Lung Adenocarcinoma.}},
author = {Jia Yang and Lanfang Li and Yunjian Pan and Wulei Hou and Xiaoyan Wang and Zhengda Li and Wenjie Wang and Yihua Sun and Ping Xu and Lifang Wang and Ying Lu and Zhongqi Wang and Zhenhui Lu and Zuoyun Wang},
journal = {International journal of biological sciences},
year = {2026},
month = oct,
doi = {10.7150/ijbs.139061},
url = {https://europepmc.org/article/MED/42910301},
note = {CC BY},
}
RIS
TY - JOUR
TI - Sanguinarine Induces Pyroptosis via the Hippo Signaling Pathway and Remodels the Tumor Immune Microenvironment in Lung Adenocarcinoma.
AU - Jia Yang
AU - Lanfang Li
AU - Yunjian Pan
AU - Wulei Hou
AU - Xiaoyan Wang
AU - Zhengda Li
AU - Wenjie Wang
AU - Yihua Sun
AU - Ping Xu
AU - Lifang Wang
AU - Ying Lu
AU - Zhongqi Wang
AU - Zhenhui Lu
AU - Zuoyun Wang
PY - 2026
DA - 2026/10/02
JO - International journal of biological sciences
DO - 10.7150/ijbs.139061
UR - https://europepmc.org/article/MED/42910301
AB - Sanguinarine (SAN), a natural alkaloid derived from Papaveraceae plants, is an active component in traditional Chinese medicines. SAN exerts inhibitory effects on tumor cells, but research on its effects on lung adenocarcinoma (LUAD) and the underlying mechanisms remains limited. The Hippo signaling pathway is commonly downregulated in LUAD, making it a key target for therapeutic intervention. Our study reveals that SAN significantly inhibits LUAD. Mechanistically, SAN bound to Large Tumor Suppressor 1 (LATS1) and promoted its phosphorylation, thereby activating the Hippo pathway and pyroptosis in LUAD. Notably, YAP overexpression inhibited pyroptosis and weakened the antitumor effect of SAN, further confirming that SAN exerts its antitumor effects by regulating the Hippo-YAP axis. Findings from both in vivo experiments and single-cell RNA sequencing consistently show that SAN remodels the tumor immune microenvironment and inhibits tumor growth. Specifically, we observed significant changes in the tumor microenvironment, including increased CD8⁺ T cell infiltration and a notably reduced number of myofibroblastic cancer-associated fibroblasts. Collectively, our findings establish SAN as a candidate therapeutic agent that exerts antitumor effects through dual modulation of the Hippo-mediated pyroptosis pathway and tumor immunity, providing a mechanistic basis for its potential clinical application in LUAD.
SN - 1449-2288
ER -