Carp protamine as a natural macromolecule for liver cancer risk reduction: Gastrointestinal bioactive peptides induce
Mengtao Cheng1, Longxing Miao2, Lu Zhang1
1School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
Abstract:
Protamine, an alkaline protein sourced from fish testes, remains underexplored for its potential application in anti-liver cancer. This study aimed to extract protamine from carp testes, evaluate its anti-liver cancer efficacy in vivo, and elucidate the underlying molecular mechanisms. Anti-tumor effects were assessed in a mouse hepatoma allograft model by measuring tumor volume and calculating tumor inhibition rates. Histopathological evaluation and immunohistochemical analysis revealed that carp protamine significantly inhibited tumor growth by inducing apoptosis in liver cancer cells. To elucidate the molecular mechanism underlying the oral efficacy of carp protamine, carp protamine hydrolysate (CPH) was generated through in vitro simulated gastrointestinal digestion. Subsequent mass spectrometric analysis identified 298 predominant peptide fragments within CPH. Network pharmacology revealed a significant association between these CPH components and the PI3K/AKT signaling pathway. Molecular docking further demonstrated strong binding affinity between ten core CPH-derived peptides and core targets in liver cancer. Western blotting confirmed significant differential expression of EGFR, p85α, and HSP90β proteins in tumor tissues from protamine-treated versus model groups. This study concludes that carp protamine is a natural macromolecule exhibiting anti-liver cancer effects, whose enzymatically derived peptides induce apoptosis in liver cancer cells through multi-target regulatory mechanisms.
Insights
Carp protamine shows anti-liver cancer potential by inducing apoptosis in cancer cells. Derived peptides target key pathways, offering a novel natural therapeutic approach for liver cancer treatment.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- Protamine, a fish-derived protein, has potential anti-liver cancer applications.
- Research into protamine's efficacy and mechanisms against liver cancer is limited.
Purpose of the Study:
- To extract carp protamine and assess its in vivo anti-liver cancer efficacy.
- To elucidate the molecular mechanisms of carp protamine's anti-tumor effects.
Main Methods:
- Assessed anti-tumor effects in a mouse hepatoma allograft model.
- Analyzed carp protamine hydrolysate (CPH) using mass spectrometry and network pharmacology.
- Investigated molecular targets via molecular docking and Western blotting.
Main Results:
- Carp protamine significantly inhibited tumor growth and induced apoptosis in liver cancer cells.
- CPH components were linked to the PI3K/AKT signaling pathway.
- Ten core CPH-derived peptides showed strong binding affinity to liver cancer targets.
- Differential expression of EGFR, p85α, and HSP90β was observed.
Conclusions:
- Carp protamine is a natural macromolecule with anti-liver cancer properties.
- Enzymatically derived peptides from carp protamine induce apoptosis via multi-target regulation.
