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L-765,314 Suppresses Melanin Synthesis by Regulating Tyrosinase Activity
Although melanin production is a key self-defense mechanism against ultraviolet radiation (UVR)-induced skin damage, uneven or excessive deposition of melanin causes hyperpigmentary disorders. Currently available whitening agents are unsatisfactory because of issues with efficacy and safety. To deve...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412649/ https://www.ncbi.nlm.nih.gov/pubmed/30795539 http://dx.doi.org/10.3390/molecules24040773 |
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author | Kim, Jinhwan Kim, Yo-Han Bang, Seunghyun Yoo, Hanju Kim, InKi Chang, Sung Eun Song, Youngsup |
author_facet | Kim, Jinhwan Kim, Yo-Han Bang, Seunghyun Yoo, Hanju Kim, InKi Chang, Sung Eun Song, Youngsup |
author_sort | Kim, Jinhwan |
collection | PubMed |
description | Although melanin production is a key self-defense mechanism against ultraviolet radiation (UVR)-induced skin damage, uneven or excessive deposition of melanin causes hyperpigmentary disorders. Currently available whitening agents are unsatisfactory because of issues with efficacy and safety. To develop more effective depigmenting agents, we performed high-throughput melanin content assay screening using the B16F10 melanoma cell line and identified L-765,314 as a drug that suppressed melanin production in cultured melanocytes in a dose-dependent manner as well as cAMP- or 12-O-tetradecanoylphorbol 13-acetate (TPA)-stimulated melanin production without cytotoxicity. Interestingly, melanogenic gene expression was not altered by L-765,314. Rather, diminished melanin production by L-765,314 appeared to be caused by downregulation of tyrosinase activity via inhibition of protein kinase C (PKC). Because L-765,314 did not show any adverse effect in melanocytes, altogether our data suggest that L-765,314 could be a potential therapeutic candidate for skin hyperpigmentary disorders and further discovery of selective inhibitors targeting PKC might be a promising strategy for the development of depigmenting agents to treat hyperpigmentary disorders. |
format | Online Article Text |
id | pubmed-6412649 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64126492019-04-09 L-765,314 Suppresses Melanin Synthesis by Regulating Tyrosinase Activity Kim, Jinhwan Kim, Yo-Han Bang, Seunghyun Yoo, Hanju Kim, InKi Chang, Sung Eun Song, Youngsup Molecules Article Although melanin production is a key self-defense mechanism against ultraviolet radiation (UVR)-induced skin damage, uneven or excessive deposition of melanin causes hyperpigmentary disorders. Currently available whitening agents are unsatisfactory because of issues with efficacy and safety. To develop more effective depigmenting agents, we performed high-throughput melanin content assay screening using the B16F10 melanoma cell line and identified L-765,314 as a drug that suppressed melanin production in cultured melanocytes in a dose-dependent manner as well as cAMP- or 12-O-tetradecanoylphorbol 13-acetate (TPA)-stimulated melanin production without cytotoxicity. Interestingly, melanogenic gene expression was not altered by L-765,314. Rather, diminished melanin production by L-765,314 appeared to be caused by downregulation of tyrosinase activity via inhibition of protein kinase C (PKC). Because L-765,314 did not show any adverse effect in melanocytes, altogether our data suggest that L-765,314 could be a potential therapeutic candidate for skin hyperpigmentary disorders and further discovery of selective inhibitors targeting PKC might be a promising strategy for the development of depigmenting agents to treat hyperpigmentary disorders. MDPI 2019-02-21 /pmc/articles/PMC6412649/ /pubmed/30795539 http://dx.doi.org/10.3390/molecules24040773 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kim, Jinhwan Kim, Yo-Han Bang, Seunghyun Yoo, Hanju Kim, InKi Chang, Sung Eun Song, Youngsup L-765,314 Suppresses Melanin Synthesis by Regulating Tyrosinase Activity |
title | L-765,314 Suppresses Melanin Synthesis by Regulating Tyrosinase Activity |
title_full | L-765,314 Suppresses Melanin Synthesis by Regulating Tyrosinase Activity |
title_fullStr | L-765,314 Suppresses Melanin Synthesis by Regulating Tyrosinase Activity |
title_full_unstemmed | L-765,314 Suppresses Melanin Synthesis by Regulating Tyrosinase Activity |
title_short | L-765,314 Suppresses Melanin Synthesis by Regulating Tyrosinase Activity |
title_sort | l-765,314 suppresses melanin synthesis by regulating tyrosinase activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412649/ https://www.ncbi.nlm.nih.gov/pubmed/30795539 http://dx.doi.org/10.3390/molecules24040773 |
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