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High-throughput, high-content screening for novel pigmentation regulators using a keratinocyte/melanocyte co-culture system

Authors
 Ju Hee Lee  ;  Hongxiang Chen  ;  Vihren Kolev  ;  Katherine H. Aull  ;  Inhee Jung  ;  Jun Wang  ;  Shoko Miyamoto  ;  Junichi Hosoi  ;  Anna Mandinova  ;  David E. Fisher 
Citation
 EXPERIMENTAL DERMATOLOGY, Vol.23(2) : 125-129, 2014 
Journal Title
 EXPERIMENTAL DERMATOLOGY 
ISSN
 0906-6705 
Issue Date
2014
MeSH
Animals ; Cell Line, Transformed ; Coculture Techniques ; Enzyme Inhibitors/isolation & purification* ; Enzyme Inhibitors/pharmacology ; Gene Expression Regulation/drug effects* ; High-Throughput Screening Assays* ; Intramolecular Oxidoreductases/biosynthesis ; Intramolecular Oxidoreductases/genetics ; Keratinocytes/drug effects* ; Keratinocytes/metabolism ; Melanins/biosynthesis* ; Melanins/genetics ; Melanocytes/drug effects* ; Melanocytes/metabolism ; Melanoma, Experimental/pathology ; Membrane Glycoproteins/biosynthesis ; Membrane Glycoproteins/genetics ; Mice ; Microphthalmia-Associated Transcription Factor/biosynthesis ; Microphthalmia-Associated Transcription Factor/genetics ; Monophenol Monooxygenase/biosynthesis ; Monophenol Monooxygenase/genetics ; Oxidoreductases/biosynthesis ; Oxidoreductases/genetics ; Skin Pigmentation/drug effects*
Keywords
co-culture ; high-content screening ; keratinocyte ; melanocyte ; microphthalmia transcription factor ; pigmentation
Abstract
Skin pigmentation is a complex process including melanogenesis within melanocytes and melanin transfer to the keratinocytes. To develop a comprehensive screening method for novel pigmentation regulators, we used immortalized melanocytes and keratinocytes in co-culture to screen large numbers of compounds. High-throughput screening plates were subjected to digital automated microscopy to quantify the pigmentation via brightfield microscopy. Compounds with pigment suppression were secondarily tested for their effects on expression of microphthalmia transcription factor (MITF) and several pigment regulatory genes, and further validated in terms of non-toxicity to keratinocytes/melanocytes and dose-dependent activity. The results demonstrate a high-throughput, high-content screening approach, which is applicable to the analysis of large chemical libraries using a co-culture system. We identified candidate pigmentation inhibitors from 4000 screened compounds including zoxazolamine, 3-methoxycatechol and alpha-mangostin, which were also shown to modulate expression of MITF and several key pigmentation factors and are worthy of further evaluation for potential translation to clinical use.
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/exd.12322/abstract
DOI
10.1111/exd.12322
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Ju Hee(이주희) ORCID logo https://orcid.org/0000-0002-1739-5956
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98482
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