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Study on the anticancer function and mechanism of cathelicidin-DM in liver cancer
Huang Hu1, Jingjing Tai1, Ruiyun Zhang2
1School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, China; Jinhua University of Vocational Technology, Agriculture College, Jinhua 321016, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Cathelicidin-DM (C-DM), a peptide from toad skin, effectively inhibits liver cancer (LC) cell growth and migration. C-DM shows promise as a novel therapeutic agent by downregulating DHRS3 and the JAK-STAT pathway.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Bioactive molecules from toad skin exhibit anticancer properties.
- Cathelicidin-DM (C-DM) is a toad skin peptide with unknown effects on tumor cells.
Purpose of the Study:
- To investigate the anti-tumor effects of C-DM on liver cancer (LC) cells.
- To elucidate the molecular mechanisms underlying C-DM's action in LC.
Main Methods:
- Cell viability assays (CCK-8), colony formation, flow cytometry, and Transwell assays were used to assess C-DM's impact on LC cells.
- Xenograft models evaluated C-DM's in vivo anti-tumor activity.
- RNA-seq and Gene Set Enrichment Analysis (GSEA) identified differentially expressed genes (DEGs) and pathways.
Main Results:
- C-DM significantly inhibited proliferation, migration, invasion, and cell cycle progression while promoting apoptosis in HepG2 and Hep3B cells.
- In vivo studies confirmed C-DM's anti-tumor efficacy with low toxicity.
- C-DM downregulated DHRS3, which was found to promote LC malignancy and activate the JAK-STAT pathway.
Conclusions:
- C-DM demonstrates significant anti-liver cancer effects.
- The mechanism involves downregulating DHRS3 and inhibiting the JAK-STAT pathway.
- C-DM represents a potential therapeutic candidate for liver cancer treatment.
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