Potential of Epidermal Growth Factor-like Peptide from the Sea Cucumber Stichopus horrens to Increase the Growth of Human Cells: In Silico Molecular Docking Approach

• Published in: Marine drugs 2022-09, Vol.20 (10), p.596
• Main Authors: Pilus, Nur Shazwani Mohd, Muhamad, Azira, Shahidan, Muhammad Ashraf, Yusof, Nurul Yuziana Mohd
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Actin; Amino acids; Bioprocessing; Body organs; Calcium; Cell cycle; Cell differentiation; Cell growth; Cell proliferation; Cells; Crystal structure; Cytoskeleton; docking; EGF-like; EGFR; Epidermal growth factor; Expulsion; Gene expression; Growth factors; Janus kinase; Kinases; MAP kinase; Marine invertebrates; Melanoma; Molecular docking; Peptides; Phospholipase C; Proliferation; Protein kinase; Proteins; protein–protein interaction; Receptors; Regeneration (biological); sea cucumber; Signal transduction; Simulation; Stichopus horrens; Survival; Tissue engineering; Transcription; Transcriptomes; Transducers; Wound healing
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md20100596

The sea cucumber is prominent as a traditional remedy among Asians for wound healing due to its high capacity for regeneration after expulsion of its internal organs. A short peptide consisting of 45 amino acids from transcriptome data of Stichopus horrens (Sh-EGFl-1) shows a convincing capability to promote the growth of human melanoma cells. Molecular docking of Sh-EGFl-1 peptide with human epidermal growth factor receptor (hEGFR) exhibited a favorable intermolecular interaction, where most of the Sh-EGFl-1 residues interacted with calcium binding-like domains. A superimposed image of the docked structure against a human EGF–EGFR crystal model also gave an acceptable root mean square deviation (RMSD) value of less than 1.5 Å. Human cell growth was significantly improved by Sh-EGFl-1 peptide at a lower concentration in a cell proliferation assay. Gene expression profiling of the cells indicated that Sh-EGFl-1 has activates hEGFR through five epidermal growth factor signaling pathways; phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), phospholipase C gamma (PLC-gamma), Janus kinase-signal transducer and activator of transcription (JAK-STAT) and Ras homologous (Rho) pathways. All these pathways triggered cells’ proliferation, differentiation, survival and re-organization of the actin cytoskeleton. Overall, this marine-derived, bioactive peptide has the capability to promote proliferation and could be further explored as a cell-growth-promoting agent for biomedical and bioprocessing applications.