Anticancer effects of alpha-helical peptide epinecidin-1 and its variants in combination with doxorubicin
Abstract
In this study, we evaluated the in silico and in vitro anticancer activity of the antimicrobial peptide epinecidin-1 (Epi-1) and its lysine-substituted variants (Variant-1 (Var-1) & Variant-2 (Var-2)). Computational docking demonstrated energetically favourable and structurally consistent interactions between the peptides and cancer-associated receptors (MerTK (PDB ID: 7OLX), EphA3 (PDB ID: 2QO9), TGF-β receptor I/ ALK5 (PDB ID: 3TZM), TrkA / NTRK1 (PDB ID: 4AOJ), and progesterone receptor (PDB ID: 1A28)), with distinct binding orientations and interaction profiles observed across the variants. Molecular dynamics simulation further substantiated these findings by confirming the stability of the selected receptor-ligand complex, with consistent root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), and intermolecular hydrogen-bond interactions profiles indicating sustained interaction integrity under dynamic conditions. The in vitro antiproliferative activity of Epi-1 and its variants was assessed by MTT assays against A549, HeLa, HepG2, IMR-32 and MCF-7 cell lines. Both variants exhibited a two- to four-fold increase in cytotoxic activity compared with native Epi-1. We also evaluated the combinational activity of each peptide with doxorubicin, where peptide-doxorubicin treatments resulted in effective cancer cell killing at reduced drug concentrations relative to individual treatments, the…
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