title: ArgTX-636, a polyamine isolated from spider venom: A novel class of melanogenesis inhibitors.
abstract: To discover new molecules with an inhibitory activity of melanogenesis a hundred of scorpions, snakes, spiders and amphibians venoms were screened for their capacity to inhibit mushroom tyrosinase using 3,4-l-dihydroxyphenylalanine (l-DOPA) as substrate. The Argiope lobata spider venom proved to be the most active. HPLC fraction containing Argiotoxine-636 (ArgTX-636), a polyamine known for its numerous biological activities, was found to also show a good regulation activity of melanogenesis by inhibiting DOPA and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidases activities, wore by tyrosinase (TYR) and tyrosinase-related protein 1 (TRP-1), respectively. Our results demonstrate that ArgTX-636 reduced the mushroom tyrosinase activity in a dose-dependent way with a maximal half inhibitory concentration (IC50) value of 8.34μM, when l-DOPA is used as substrate. The Lineweaver-Burk study showed that ArgTX-636 is a mixed type inhibitor of the diphenolase activity. Moreover, ArgTX-636 inhibits DHICA oxydase activity of mushroom tyrosinase activity with IC50at 41.3μM. ArgTX-636 has no cytotoxicity in B16F10 melanoma cells at concentrations up to 42.1μM. The effect of ArgTX-636 on melanogenesis showed that melanin production in B16F10 melanoma cell decreased by approximatively 70% compared to untreated cells. ArgTX-636 displayed no significant effect on the TYR expression while the protein level of TRP-1 decreased in B16F10 cells. Thus, ArgTX-636 could have particular interest for cosmetic and/or pharmaceutical use in order to reduce important dermatoses in black and mixed skins.
authors.affiliation: Aix Marseille Univ, CNRS, ICR UMR 7273, 13397 Marseille, Cedex 20, France; Laboratoire In'Oya SAS-Pôle d'Activités Yvon Morandat, 1480 Av. d'Arménie, 13120 Gardanne, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Verdoni
authors.affiliation: Laboratoire In'Oya SAS-Pôle d'Activités Yvon Morandat, 1480 Av. d'Arménie, 13120 Gardanne, France; Aix Marseille Univ, INSERM, UMR 911, CRO2, 13385 Marseille, Cedex 5, France.
authors.forename: Hermine
authors.initials: H
authors.lastname: Roudaut
authors.affiliation: Laboratoire LATOXAN SAS, 845 avenue Pierre Brossolette, 26800 Portes lès Valence, France.
authors.forename: Harold
authors.initials: H
authors.lastname: De Pomyers
authors.affiliation: Aix Marseille Univ, CNRS, ICR UMR 7273, 13397 Marseille, Cedex 20, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Gigmes
authors.affiliation: Aix Marseille Univ, CNRS, ICR UMR 7273, 13397 Marseille, Cedex 20, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Bertin
authors.affiliation: Aix Marseille Univ, INSERM, UMR 911, CRO2, 13385 Marseille, Cedex 5, France.
authors.forename: José
authors.initials: J
authors.lastname: Luis
authors.affiliation: Laboratoire In'Oya SAS-Pôle d'Activités Yvon Morandat, 1480 Av. d'Arménie, 13120 Gardanne, France.
authors.forename: Abd Haq
authors.initials: AH
authors.lastname: Bengeloune
authors.affiliation: Aix Marseille Univ, CNRS, ICR UMR 7273, 13397 Marseille, Cedex 20, France. Electronic address: kamel.mabrouk@univ-amu.fr.
authors.forename: Kamel
authors.initials: K
authors.lastname: Mabrouk
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007210:Indoleacetic Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D011073:Polyamines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013111:Spider Venoms / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D007210:Indoleacetic Acids; D008543:Melanins; D011073:Polyamines; D013111:Spider Venoms; C558368:argiotoxin-636
keywords: ArgTX-636; Argiotoxine; DHICA oxydase activity; DOPA oxydase activity; Hyperpigmentation; Melanogenesis; Spider venoms; Tyrosinase; Tyrosinase related protein 1 (TRP-1)