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Rhododenol Activates Melanocytes and Induces Morphological Alteration at Sub-Cytotoxic Levels

Rhododenol (RD), a whitening cosmetic ingredient, was withdrawn from the market due to RD-induced leukoderma (RIL). While many attempts have been made to clarify the mechanism underlying RIL, RIL has not been fully understood yet. Indeed, affected subjects showed uneven skin pigmentation, but the fe...

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Autores principales: Kim, Minjeong, Lee, Chang-Seok, Lim, Kyung-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888388/
https://www.ncbi.nlm.nih.gov/pubmed/31726751
http://dx.doi.org/10.3390/ijms20225665
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author Kim, Minjeong
Lee, Chang-Seok
Lim, Kyung-Min
author_facet Kim, Minjeong
Lee, Chang-Seok
Lim, Kyung-Min
author_sort Kim, Minjeong
collection PubMed
description Rhododenol (RD), a whitening cosmetic ingredient, was withdrawn from the market due to RD-induced leukoderma (RIL). While many attempts have been made to clarify the mechanism underlying RIL, RIL has not been fully understood yet. Indeed, affected subjects showed uneven skin pigmentation, but the features are different from vitiligo, a skin hypopigmentary disorder, alluding to events more complex than simple melanocyte cytotoxicity. Here, we discovered that rhododenol treatment reduced the number of melanocytes in a pigmented 3D human skin model, Melanoderm™, confirming the melanocyte toxicity of RD. Of note, melanocytes that survived in the RD treated tissues exhibited altered morphology, such as extended dendrites and increased cell sizes. Consistently with this, sub-cytotoxic level of RD increased cell size and elongated dendrites in B16 melanoma cells. Morphological changes of B16 cells were further confirmed in the immunocytochemistry of treated cells for actin and tubulin. Even more provoking, RD up-regulated the expression of tyrosinase and TRP1 in the survived B16 cells. Evaluation of mRNA expression of cytoskeletal proteins suggests that RD altered the cytoskeletal dynamic favoring cell size expansion and melanosome maturation. Collectively, these results suggest that RD not only induces cytotoxicity in melanocytes but also can lead to a profound perturbation of melanocyte integrity even at sub-cytotoxic levels.
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spelling pubmed-68883882019-12-09 Rhododenol Activates Melanocytes and Induces Morphological Alteration at Sub-Cytotoxic Levels Kim, Minjeong Lee, Chang-Seok Lim, Kyung-Min Int J Mol Sci Article Rhododenol (RD), a whitening cosmetic ingredient, was withdrawn from the market due to RD-induced leukoderma (RIL). While many attempts have been made to clarify the mechanism underlying RIL, RIL has not been fully understood yet. Indeed, affected subjects showed uneven skin pigmentation, but the features are different from vitiligo, a skin hypopigmentary disorder, alluding to events more complex than simple melanocyte cytotoxicity. Here, we discovered that rhododenol treatment reduced the number of melanocytes in a pigmented 3D human skin model, Melanoderm™, confirming the melanocyte toxicity of RD. Of note, melanocytes that survived in the RD treated tissues exhibited altered morphology, such as extended dendrites and increased cell sizes. Consistently with this, sub-cytotoxic level of RD increased cell size and elongated dendrites in B16 melanoma cells. Morphological changes of B16 cells were further confirmed in the immunocytochemistry of treated cells for actin and tubulin. Even more provoking, RD up-regulated the expression of tyrosinase and TRP1 in the survived B16 cells. Evaluation of mRNA expression of cytoskeletal proteins suggests that RD altered the cytoskeletal dynamic favoring cell size expansion and melanosome maturation. Collectively, these results suggest that RD not only induces cytotoxicity in melanocytes but also can lead to a profound perturbation of melanocyte integrity even at sub-cytotoxic levels. MDPI 2019-11-12 /pmc/articles/PMC6888388/ /pubmed/31726751 http://dx.doi.org/10.3390/ijms20225665 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, Minjeong
Lee, Chang-Seok
Lim, Kyung-Min
Rhododenol Activates Melanocytes and Induces Morphological Alteration at Sub-Cytotoxic Levels
title Rhododenol Activates Melanocytes and Induces Morphological Alteration at Sub-Cytotoxic Levels
title_full Rhododenol Activates Melanocytes and Induces Morphological Alteration at Sub-Cytotoxic Levels
title_fullStr Rhododenol Activates Melanocytes and Induces Morphological Alteration at Sub-Cytotoxic Levels
title_full_unstemmed Rhododenol Activates Melanocytes and Induces Morphological Alteration at Sub-Cytotoxic Levels
title_short Rhododenol Activates Melanocytes and Induces Morphological Alteration at Sub-Cytotoxic Levels
title_sort rhododenol activates melanocytes and induces morphological alteration at sub-cytotoxic levels
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888388/
https://www.ncbi.nlm.nih.gov/pubmed/31726751
http://dx.doi.org/10.3390/ijms20225665
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