1. A Pleurocidin-Like Peptide from Poecilia Mexicana Fish Induces Selective Cytotoxicity in Leukemia Jurkat Cells Through The Apoptosis Pathway
Mostafa Ebrahimdoost, Mohsen Mohammadi, Narges Obeidi, Seyed Amin Mohammadi, Gholamreza Khamisipour Cell J. 2023 Feb 1;25(2):76-84. doi: 10.22074/cellj.2022.557529.1062.
Objective: Some cationic anti-microbial peptides show a wide range of cytotoxic action versus malignant cells, which may lead to developing a novel group of antitumor medications. In the present study, the anticancer activity of pleurocidin-like peptide WF3 isoform X2 (AMP-WF3), from the Poecilia Mexicana fish, against leukemic cell line Jurkat was evaluated, and the cytotoxicity compared with the effects on normal cells, including peripheral blood mononuclear cells (PBMCs) and human dermal fibroblast (HDF) cells. Materials and methods: In this experimental study, cells were treated with various dosages of AMP-WF3 for 24 hours. Using methyl thiazole tetrazolium salt reduction (MTT test), the effects of the AMP-WF3 on cell viability and toxicity were evaluated. The impact of this peptide on apoptotic pathways was examined using flow cytometry and Annexin V-PI stains. Additionally, the relative expression of the P53, P21 and BCL-2 genes was evaluated using a real-time polymerase chain reaction. Results: The Jurkat cell line was more susceptible to AMP-WF3 cytotoxicity [half-maximal inhibitory concentration (IC50)=50 μM], while normal cells (PBMCs and HDF) were less susceptible. Flow cytometry verified that the apoptotic activity of AMP-WF3 on Jurkat cells was significantly higher than that of HDF and PBMCs. Peptide-treated Jurkat cells were associated with increased expression of P21, and P53 genes. In contrast, the changes in P21, P53, and BCL-2 genes differed in PBMCs and HDF cells. In HDF cells, simultaneous increase of P21, P53, and BCL-2, and in PBMCs, only the increase of BCL-2 was observed. Conclusion: Our research showed that AMP-WF3 could be developed as a novel treatment agent with minimum side effects for ALL patients.
2. Interaction of pleurocidin and its analogs with phospholipid membrane and their antibacterial activity
K Yoshida, Y Mukai, T Niidome, C Takashi, Y Tokunaga, T Hatakeyama, H Aoyagi J Pept Res. 2001 Feb;57(2):119-26. doi: 10.1034/j.1399-3011.2001.00802.x.
A 25-mer cationic peptide pleurocidin, isolated from the winter flounder, has broad antibacterial activity. To clarify the structure-activity relationship, its properties and biological activity were examined. CD measurements showed that pleurocidin took an alpha-helical structure in the presence of DOPC/DOPG (3:1, anionic) vesicles. Very weak hemolytic activity of pleurocidin was observed and its antibacterial activity was moderate. Tryptophan fluorescence shift measurements showed that pleurocidin interacted weakly with a neutral phospholipid, but strongly with an acidic phospholipid. The peptide exhibited weak dye-leakage activity for DOPC (neutral) vesicles and moderate activity for acidic vesicles. From experiments on dye-leakage activity and membrane translocation of the peptide, it seemed likely that pleurocidin, like magainin 2, forms pores in the lipid membrane. A study of amino acid substitution in pleurocidin revealed that alpha-helicity, rather than hydrophobicity, affects the properties and activity of the peptide.
3. Molecular modelling and docking analysis of pleurocidin (an antimicrobial peptide) like peptides with enterotoxin H from Klebsilla pneumonia
Giridharan Bupesh, et al. Bioinformation. 2019 Dec 17;15(11):838-844. doi: 10.6026/97320630015838. eCollection 2019.
Enterotoxin H is a key molecular target for replication and establishment of Klebsilla pneumonia in the host. Therefore, it is of interest to study the interaction of enterotoxin H with pleurocidin like peptides using molecular modelling (template PDB ID: 1YCE), Lig-Plot (ligand construction) and docking tools for therapeutic consideration. The hydrophobic pocket and the active site residues (Val 13, Met 16, Gly 25, Ala 25, and Ile 28) were identified using Cast P, Molegro and Sitehound tools. Docking results show that the pleurocidin like peptides interacts with the active sites of enterotoxin H with 300.96 docking score with optimal binding features.
