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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Rhododenol (RD), a whitening cosmetic ingredient, was withdrawn from the market due to RD-induced leukoderma (RIL).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...
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/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description | Rhododenol (RD), a whitening cosmetic ingredient, was withdrawn from the market due to RD-induced leukoderma (RIL).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. |
format | Online Article Text |
id | pubmed-6888388 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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