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
  • 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. [email protected].
  • 6. Cancer Research Institute, First People's Hospital of Foshan, Foshan, 528000, Guangdong, China. [email protected].
  • 7. School of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore BC, QLD, 4558, Australia. [email protected].
  • 8. Centre for Bioinnovation, University of the Sunshine Coast, Maroochydore BC, QLD, 4558, Australia. [email protected].
  • 9. Cancer Research Institute, First People's Hospital of Foshan, Foshan, 528000, Guangdong, China. [email protected].
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.
Products