title: Galvanic zinc-copper microparticles inhibit melanogenesis via multiple pigmentary pathways.
abstract: The endogenous electrical field of human skin plays an important role in many skin functions. However, the biological effects and mechanism of action of externally applied electrical stimulation on skin remain unclear. Recent study showed that galvanic zinc-copper microparticles produce electrical stimulation and reduce inflammatory and immune responses in intact skin, suggesting the important role of electrical stimulation in non-wounded skin. The objective of this study is to investigate the biological effect of galvanic zinc-copper microparticles on skin pigmentation. Our findings showed that galvanic zinc-copper microparticles inhibited melanogenesis in a human melanoma cell line (MNT-1), human keratinocytes and melanoma cells co-cultures, and in pigmented epidermal equivalents. Treatment of galvanic zinc-copper microparticles inhibited melanogenesis by reducing the promoter transactivation of tyrosinase and tyrosinase-related protein-1 in human melanoma cells. In a co-culture Transwell system of keratinocytes and melanoma cells, galvanic zinc-copper microparticles reduced melanin production via downregulation of endothelin-1 secretion from keratinocytes and reduced tyrosinase gene expression in melanoma cells. In addition, exposure of pigmented epidermal equivalents to galvanic zinc-copper microparticles resulted in reduced melanin deposition. In conclusion, our data demonstrated for the first time that galvanic zinc-copper microparticles reduced melanogenesis in melanoma cells and melanin deposition in pigmented epidermal equivalents by affecting multiple pigmentary pathways.
authors.affiliation: Johnson & Johnson Asia Pacific, 51 Science Park Road, #01-01/05 The Aries, Singapore Science Park 2, Singapore, 117586, Republic of Singapore, ywon@its.jnj.com.
authors.forename: Yen-Kim
authors.initials: YK
authors.lastname: Won
authors.forename: Connie B
authors.initials: CB
authors.lastname: Lin
authors.forename: Miri
authors.initials: M
authors.lastname: Seiberg
authors.forename: Nannan
authors.initials: N
authors.lastname: Chen
authors.forename: Yaping
authors.initials: Y
authors.lastname: Hu
authors.forename: Dianne
authors.initials: D
authors.lastname: Rossetti
authors.forename: Claude
authors.initials: C
authors.lastname: Saliou
authors.forename: Chong-Jin
authors.initials: CJ
authors.lastname: Loy
mesh_terms: D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D018920:Coculture Techniques; D003300:Copper / Q000494:pharmacology*; D015536:Down-Regulation; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy / Q000517:prevention & control; D053768:Metal Nanoparticles / Q000627:therapeutic use*; D014442:Monophenol Monooxygenase / Q000096:biosynthesis / Q000235:genetics; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012880:Skin Pigmentation / Q000187:drug effects* / Q000502:physiology; D015032:Zinc / Q000494:pharmacology*
chemical_list: D019332:Endothelin-1; D008543:Melanins; D003300:Copper; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D015032:Zinc