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

Abstract 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 explo...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-96438-0
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author 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
author_facet 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
author_sort Yuandong Luo
collection DOAJ
description Abstract 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.
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spelling doaj-art-d8bb6de964bd4d4db169f718f7b9d1352025-08-20T03:18:38ZengNature PortfolioScientific Reports2045-23222025-04-0115111310.1038/s41598-025-96438-0Caerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cellsYuandong Luo0Junjie Li1Quanlan Fu2Pingping Zhang3Xinyi Song4Mengqi Liu5Rongmi Mo6Jiawei Fu7Shuxian Tang8Jialing Wu9Xiaodan Yang10Xiaosong Liu11Tianfang Wang12Guoying Ni13Medical College of Guizhou UniversityZhongao Biomedical Technology (Guangdong) Co. LtdMedical College of Guizhou UniversityCancer Research Institute, First People’s Hospital of FoshanThe First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical UniversityMedical College of Guizhou UniversityThe First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical UniversityThe First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical UniversityCancer Research Institute, First People’s Hospital of FoshanCancer Research Institute, First People’s Hospital of FoshanThe First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical UniversityMedical College of Guizhou UniversitySchool of Science, Technology and Engineering, University of the Sunshine CoastCancer Research Institute, First People’s Hospital of FoshanAbstract 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.https://doi.org/10.1038/s41598-025-96438-0Caerin peptidePyroptosisCaspase 3/GSDME signalling pathwayIL-18Lactate dehydrogenase
spellingShingle 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
Caerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells
Scientific Reports
Caerin peptide
Pyroptosis
Caspase 3/GSDME signalling pathway
IL-18
Lactate dehydrogenase
title Caerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells
title_full Caerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells
title_fullStr Caerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells
title_full_unstemmed Caerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells
title_short Caerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells
title_sort caerin 1 1 and 1 9 peptides induce acute caspase 3 gsdme mediated pyroptosis in epithelial cancer cells
topic Caerin peptide
Pyroptosis
Caspase 3/GSDME signalling pathway
IL-18
Lactate dehydrogenase
url https://doi.org/10.1038/s41598-025-96438-0
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