Investigating the anticancer effect of purified rCec-B peptide in a DEN murine model: Insights into tumorigenesis prevention, bioavailability, and molecular mechanisms.

[BACKGROUND] Anticancer peptides (ACPs) are considered cancer therapeutic candidates through decreasing tumor cell proliferation, migration, and angiogenesis.

[OBJECTIVES] Determine the therapeutic potential of purified recombinant cecropin-B (rCec-B) peptide in vivo on HCC murine model and its effect, particularly on the activation of apoptotic pathways.

[METHODS] Intact mass analysis of rCec-B was confirmed using mass spectrometry, molecular docking on epidermal growth factor receptor (EGFR) apoptosis was studied, and an in vivo acute toxicity study, followed by establishing the HCC model using diethylnitrosamine (DEN) was performed. Biochemical, molecular, and immunohistochemical parameters were detected in serum and liver samples.

[RESULTS] A molecular docking study on EGFR showed a predicted binding model of rCec-B as a ligand with a high binding affinity equal to -50.167 kcal/mol. The peptide showed remarkable safety in the studied high doses. The liver of the HCC untreated model had a distorted lobular pattern with minimal to mild nuclear atypia. In HCC treated with rCec-B, liver sections had periportal inflammation, hydropic degeneration with focal cholestasis, and apoptotic hepatocellular bodies. Molecular detection and immunohistochemical analysis showed an upregulation of the oncogenic marker, Bcl-2, and a downregulation of apoptotic markers (FAS, FAS-L, Cas-8, BAX, and BID) in the untreated DEN group. Treated groups had a significant increase in all the detected apoptotic markers.

[CONCLUSION] This study sheds light on the potential rCec-B's role in suppressing HCC progression. Hence, this peptide could be considered a promising therapeutic drug alone or in combination with other drugs to alleviate HCC treatment.