title: Potential therapeutic applications of multifunctional host-defense peptides from frog skin as anti-cancer, anti-viral, immunomodulatory, and anti-diabetic agents.
abstract: Frog skin constitutes a rich source of peptides with a wide range of biological properties. These include host-defense peptides with cytotoxic activities against bacteria, fungi, protozoa, viruses, and mammalian cells. Several hundred such peptides from diverse species have been described. Although attention has been focused mainly on antimicrobial activity, the therapeutic potential of frog skin peptides as anti-infective agents remains to be realized and no compound based upon their structures has yet been adopted in clinical practice. Consequently, alternative applications are being explored. Certain naturally occurring frog skin peptides, and analogs with improved therapeutic properties, show selective cytotoxicity against tumor cells and viruses and so have potential for development into anti-cancer and anti-viral agents. Some peptides display complex cytokine-mediated immunomodulatory properties. Effects on the production of both pro-inflammatory and anti-inflammatory cytokines by peritoneal macrophages and peripheral blood mononuclear cells have been observed so that clinical applications as anti-inflammatory, immunosuppressive, and immunostimulatory agents are possible. Several frog skin peptides, first identified on the basis of antimicrobial activity, have been shown to stimulate insulin release both in vitro and in vivo and so show potential as incretin-based therapies for treatment of patients with Type 2 diabetes mellitus. This review assesses the therapeutic possibilities of peptides from frogs belonging to the Ascaphidae, Alytidae, Pipidae, Dicroglossidae, Leptodactylidae, Hylidae, and Ranidae families that complement their potential role as anti-infectives for use against multidrug-resistant microorganisms.
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, 17666 Al Ain, United Arab Emirates; School of Biomedical Sciences, University of Ulster, Cromore Road, Coleraine, Northern Ireland BT52 1SA, UK. Electronic address: jmconlon@uaeu.ac.ae.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Conlon
authors.affiliation: Department of Biochemistry, College of Medicine and Health Sciences, United Arab Emirates University, 17666 Al Ain, United Arab Emirates.
authors.forename: Milena
authors.initials: M
authors.lastname: Mechkarska
authors.affiliation: Center for Molecular Medicine, Faculty of Medicine, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Miodrag L
authors.initials: ML
authors.lastname: Lukic
authors.affiliation: School of Biomedical Sciences, University of Ulster, Cromore Road, Coleraine, Northern Ireland BT52 1SA, UK.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use; D001001:Anura; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D056747:Immunomodulation / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy*; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D011898:Ranidae; D012867:Skin / Q000378:metabolism; D014780:Viruses / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D010455:Peptides
keywords: Anti-cancer; Anti-viral; Frog skin; Host-defense peptide; Immunomodulatory; Type 2 diabetes