biostudies-literatureLuo YGuangdong Provincial Department of Science and TechnologyNational Natural Science Foundation of Chinathe Deng Feng Project of First People's Hospital of Foshanthe Deng Feng Project of First People’s Hospital of Foshan13377https://www.ebi.ac.uk/biostudies/studies/S-EPMC12008296biostudies-literatureUnknown15(1)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 upregulatScientific reportsCaerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells.PMC12008296319713552016A0202130012019A008Fu QWu JLi JLiu MNi GZhang PMo RYang XLiu XWang TFu JTang SLuo YSong XfalseCaerin 1.1 and 1.9 peptides induce acute caspase 3/GSDME-mediated pyroptosis in epithelial cancer cells.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 upregulat2025-01-01T00:00:00Z2025 Apr2025-06-28T03:05:31.876Z2025-06-28T03:05:31.876ZS-EPMC120082964025120810.1038/s41598-025-96438-0