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

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

  • Sci Rep. 2025 Apr 18;15(1):13377. doi: 10.1038/s41598-025-96438-0.
Yuandong Luo 1,  Junjie Li 2,  Quanlan Fu 1,  Pingping Zhang 3,  Xinyi Song 4,  Mengqi Liu 1,  Rongmi Mo 4,  Jiawei Fu 4,  Shuxian Tang 3,  Jialing Wu 3,  Xiaodan Yang 4,  Xiaosong Liu 5 6,  Tianfang Wang 7 8,  Guoying Ni 9
Affiliations

Affiliations

  • 1 Medical College of Guizhou University, Guiyang, 550025, Guizhou, China.
  • 2 Zhongao Biomedical Technology (Guangdong) Co. Ltd, Zhongshan, 528400, Guangdong, China.
  • 3 Cancer Research Institute, First People's Hospital of Foshan, Foshan, 528000, Guangdong, China.
  • 4 The First Affiliated Hospital/Clinical Medical School, Guangdong Pharmaceutical University, Guangzhou, 510080, China.
  • 5 Medical College of Guizhou University, Guiyang, 550025, Guizhou, China. xiaosongl@yahoo.com.
  • 6 Cancer Research Institute, First People's Hospital of Foshan, Foshan, 528000, Guangdong, China. xiaosongl@yahoo.com.
  • 7 School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore BC, QLD, 4558, Australia. twang@usc.edu.au.
  • 8 Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore BC, QLD, 4558, Australia. twang@usc.edu.au.
  • 9 Cancer Research Institute, First People's Hospital of Foshan, Foshan, 528000, Guangdong, China. ngy2003@gmail.com.
PMID: 40251208 DOI: 10.1038/s41598-025-96438-0
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.

Keywords

Caerin peptide; Caspase 3/GSDME signalling pathway; IL-18; Lactate dehydrogenase; Pyroptosis.

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