Study on the anticancer function and mechanism of cathelicidin-DM in liver cancer

• Published in: Genomics (San Diego, Calif.) Vol. 117; no. 3; p. 111049
• Main Authors: Hu, Huang, Tai, Jingjing, Zhang, Ruiyun, Zhang, Hong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2025
• Subjects: Animals; Antimicrobial Cationic Peptides - pharmacology; antineoplastic activity; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; apoptosis; Apoptosis - drug effects; C-DM; Cathelicidins - pharmacology; cell cycle; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; DHRS3; drugs; flow cytometry; gene expression regulation; genomics; Hep G2 Cells; Humans; JAK-STAT pathway; Liver cancer; liver neoplasms; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Mice; peptides; phenotype; sequence analysis; toads; toxicity; viability; xenotransplantation; Liver cancer; C-DM; DHRS3; JAK-STAT pathway
• ISSN: 0888-7543; 1089-8646; 1089-8646
• DOI: 10.1016/j.ygeno.2025.111049

Previous studies have shown that bioactive molecules secreted by toad skin possess anticancer properties. Cathelicidin-DM (C-DM) is a bioactive peptide secreted by toad skin, but its effects on tumor cells and the underlying molecular mechanisms remain unknown. The impact of varying amphibian peptides on the viability of various tumor cells was determined by CCK-8. The influence of C-DM on liver cancer (LC) cell function was investigated using colony formation, flow cytometry, and Transwell. The anti-tumor activity of C-DM was evaluated by xenograft models. RNA-seq was done to confirm differentially expressed genes (DEGs), which were subject to GSEA. Cellular experiments were performed to verify the molecular regulatory mechanism of C-DM in LC. C-DM (100 μg/mL) had a significant repressive impact on the proliferation, migration, invasion, and cell cycle progression of HepG2 and Hep3B cells, and facilitated apoptosis. In vivo experiments validated the anti-tumor impact of C-DM, while its toxicity was low. DEG DHRS3 was enriched in the JAK-STAT pathway. Overexpression of DHRS3 fostered the malignant phenotype of LC cells and activated the JAK-STAT pathway. However, the addition of C-DM weakened the oncogenic properties of DHRS3 and repressed the JAK-STAT pathway. C-DM exerted an anti-LC effect by downregulating DHRS3 and mediating the JAK-STAT pathway, indicating that C-DM may be a promising candidate drug for LC treatment. •This study confirmed the anti-tumor activity of cathelicidin-DM on liver cancer cells.•DHRS3 is identified as a key oncogenic driver in liver cancer, promoting malignant phenotypes via activation of the JAK-STAT signaling pathway.•C-DM antagonizes DHRS3-mediated JAK-STAT pathway activation, revealing a novel molecular mechanism for its anti-tumor efficacy.