Caerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells

Yuandong Luo; Junjie Li; Quanlan Fu; Pingping Zhang; Xinyi Song; Mengqi Liu; Rongmi Mo; Jiawei Fu; Shuxian Tang; Jialing Wu; Xiaodan Yang; Xiaosong Liu; Tianfang Wang; Guoying Ni

doi:10.1038/s41598-025-96438-0

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Caerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells

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Caerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells

Yuandong Luo, Junjie Li, Quanlan Fu, Pingping Zhang, Xinyi Song, Mengqi Liu, Rongmi Mo, Jiawei Fu, Shuxian Tang, Jialing Wu, …

Scientific Reports, Vol.15(1), pp.1-13

2025

DOI: https://doi.org/10.1038/s41598-025-96438-0

PMID: 40251208

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Abstract

cancer immunotherapy

cell death

cell death and immune response

cervical cancer

molecular medicine

peptides

stress signalling

translational resaearch

caerin peptide

pyroptosis

caspase 3/GSDME signalling pathway

IL-18

lactate dehydrogenase

UniSC Diversity Area - Life Stages

Caerin peptides exhibit a dual role in cancer treatment by directly killing cancer cells and modulating the tumour microenvironment to enhance anti-tumour immunity. This study investigates the mechanisms underlying caerin 1.1/1.9-induced acute cell death in epithelial cancer cells and explores their therapeutic potential. HeLa, A549, and Huh-7 cancer cell lines were treated with caerin 1.1/1.9 peptides. Morphological observations, flow cytometry, lactate dehydrogenase (LDH) release, and IL-18 secretion assays revealed the occurrence of pyroptosis following treatment. Specifically, a 1-h treatment with caerin 1.1/1.9 induced pyroptosis in HeLa, A549, and Huh-7 cells, characterised by cell swelling, membrane bubbling, and the release of IL-18 and LDH. Western blotting confirmed the upregulation of pyroptosis markers, including caspase-3, cleaved caspase-3, and GSDME-N fragments. These findings highlight the significant role of caerin peptides in inducing acute pyroptosis, a form of programmed cell death that enhances the immunogenicity of dying cancer cells, thus potentially improving the effectiveness of immunotherapies. This research underscores the therapeutic potential of caerin 1.1/1.9 peptides in cancer treatment, providing a foundation for developing new anti-cancer strategies that leverage both direct cytotoxic effects and immune modulation to achieve more effective and sustained anti-tumour responses.

Details

Title: Caerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells
Authors: Yuandong Luo - Guizhou University
Junjie Li - Zhongao Biomedical Technology (China)
Quanlan Fu - Guizhou University
Pingping Zhang - First People's Hospital of Foshan
Xinyi Song - Guangdong Pharmaceutical University
Mengqi Liu - Guizhou University
Rongmi Mo - Guangdong Pharmaceutical University
Jiawei Fu - Guangdong Pharmaceutical University
Shuxian Tang - First People's Hospital of Foshan
Jialing Wu - First People's Hospital of Foshan
Xiaodan Yang - Guangdong Pharmaceutical University
Xiaosong Liu (Corresponding Author) - First People's Hospital of Foshan
Tianfang Wang (Corresponding Author) - University of the Sunshine Coast, Queensland, School of Science, Technology and Engineering
Guoying Ni (Corresponding Author) - First People's Hospital of Foshan
Publication details: Scientific Reports, Vol.15(1), pp.1-13
Publisher: Nature Publishing Group
Date published: 2025
DOI: 10.1038/s41598-025-96438-0
ISSN: 2045-2322
PMID: 40251208
Copyright note: This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Data Availability: Data is provided within the manuscript or supplementary information files. For additional data requests, please contact Dr. Guoying Ni at ngy2003@gmail.com.
Grant note: Guangdong Science and Technology Department (2016A020213001), the Deng Feng Project of First People’s Hospital of Foshan (2019A008), National Natural Science Foundation of China (31971355).
Organisation Unit: School of Science and Engineering - Legacy; GeneCology Research Centre - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 991121900902621
Output Type: Journal article

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