A Pleurocidin-Like Peptide from Poecilia Mexicana Fish Induces Selective Cytotoxicity in Leukemia Jurkat Cells Through The Apoptosis Pathway

Abstract

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. © 2023 Royan Institute (ACECR). All rights reserved