title: Effective inhibition of melanosome transfer to keratinocytes by lectins and niacinamide is reversible.
abstract: Skin pigmentation results in part from the transfer of melanized melanosomes synthesized by melanocytes to neighboring keratinocytes. Plasma membrane lectins and their glycoconjugates expressed by these epidermal cells are critical molecules involved in this transfer process. In addition, the derivative of vitamin B(3), niacinamide, can inhibit melanosome transfer and induce skin lightening. We investigated the effects of these molecules on the viability of melanocytes and keratinocytes and on the reversibility of melanosome-transfer inhibition induced by these agents using an in vitro melanocyte-keratinocyte coculture model system. While lectins and neoglycoproteins could induce apoptosis in a dose-dependent manner to melanocytes or keratinocytes in monoculture, similar dosages of the lectins, as opposed to neoglycoproteins, did not induce apoptosis to either cell type when treated in coculture. The dosages of lectins and niacinamide not affecting cell viability produced an inhibitory effect on melanosome transfer, when used either alone or together in cocultures of melanocytes-keratinocytes. Cocultures treated with lectins or niacinamide resumed normal melanosome transfer in 3 days after removal of the inhibitor, while cocultures treated with a combination of lectins and niacinamide demonstrated a lag in this recovery. Subsequently, we assessed the effect of niacinamide on facial hyperpigmented spots using a vehicle-controlled, split-faced design human clinical trial. Topical application of niacinamide resulted in a dose-dependent and reversible reduction in hyperpigmented lesions. These results suggest that lectins and niacinamide at concentrations that do not affect cell viability are reversible inhibitors of melanosome transfer.
authors.affiliation: Department of Dermatology, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Greatens
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Hakozaki
authors.forename: Amy
authors.initials: A
authors.lastname: Koshoffer
authors.forename: Howard
authors.initials: H
authors.lastname: Epstein
authors.forename: Sandy
authors.initials: S
authors.lastname: Schwemberger
authors.forename: George
authors.initials: G
authors.lastname: Babcock
authors.forename: Donald
authors.initials: D
authors.lastname: Bissett
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Takiwaki
authors.forename: Seiji
authors.initials: S
authors.lastname: Arase
authors.forename: R Randall
authors.initials: RR
authors.lastname: Wickett
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Boissy
mesh_terms: D000287:Administration, Topical; D000328:Adult; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D017495:Hyperpigmentation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D037102:Lectins / Q000494:pharmacology*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020460:Melanosomes / Q000187:drug effects* / Q000378:metabolism*; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D012880:Skin Pigmentation / Q000187:drug effects / Q000502:physiology
chemical_list: D037102:Lectins; D009536:Niacinamide