title: Aliphatic and alicyclic diols induce melanogenesis in cultured cells and guinea pig skin.
abstract: We have found that several aliphatic and alicyclic diols induce melanogenesis in cultured S91 mouse melanoma cells and normal human epidermal melanocytes (NHEM). In addition, these compounds induce melanogenesis when applied to guinea pig skin, with transfer of melanin to keratinocytes and formation of "supranuclear caps," as occurs in naturally pigmented skin. The relative order of potency of some of these diols in NHEM is 5-norbornene-2,2-dimethanol > 3,3-dimethyl-1,2-butanediol > cis-1,2-cyclopentanediol > 2,3-dimethyl-2,3-butanediol > 1,2-propanediol. Following treatment with these diols or 3-isobutyl-1-methylxanthine, melanin and tyrosinase activity are increased within S91 cells and NHEM; however, for cultured NHEM, the largest increases of melanin and tyrosinase occur in an extracellular particulate fraction, shown by electron microscopy to consist almost entirely of stage III and IV melanosomes. These results indicate that cultured NHEM treated with diols export melanosomes in a fashion that is commensurate with natural melanogenic processes. In contrast, S91 mouse melanoma cells exhibit aberrant melanosomal trafficking, in accordance with the known defect in myosin-V mediated melanosomal transport. Both S91 cells and NHEM exhibit morphologic changes and growth arrest indicative of differentiation following treatment with diols. The diols described in this report are candidates for use as cosmeceutical tanning agents.
authors.affiliation: Codon Pharmaceuticals, Gaithersburg, Maryland 20877, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Brown
authors.forename: W Y
authors.initials: WY
authors.lastname: Ren
authors.forename: A
authors.initials: A
authors.lastname: Khorlin
authors.forename: K
authors.initials: K
authors.lastname: Lesiak
authors.forename: D
authors.initials: D
authors.lastname: Conklin
authors.forename: K A
authors.initials: KA
authors.lastname: Watanabe
authors.forename: M M
authors.initials: MM
authors.lastname: Seidman
authors.forename: J
authors.initials: J
authors.lastname: George
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000648:ultrastructure; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000378:metabolism / Q000648:ultrastructure; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D012016:Reference Values; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D008543:Melanins; D014442:Monophenol Monooxygenase