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Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model

Paclitaxel is a microtubule-stabilizing chemotherapeutic agent approved for the treatment of ovarian, non-small cell lung, head, neck, and breast cancers. Despite its beneficial effects on cancer and widespread use, paclitaxel also damages healthy tissues, including the skin. However, the mechanisms...

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Autores principales: Montero, Paula, Milara, Javier, Pérez-Leal, Martín, Estornut, Cristina, Roger, Inés, Pérez-Fidalgo, Alejandro, Sanz, Celia, Cortijo, Julio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834980/
https://www.ncbi.nlm.nih.gov/pubmed/35163066
http://dx.doi.org/10.3390/ijms23031142
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author Montero, Paula
Milara, Javier
Pérez-Leal, Martín
Estornut, Cristina
Roger, Inés
Pérez-Fidalgo, Alejandro
Sanz, Celia
Cortijo, Julio
author_facet Montero, Paula
Milara, Javier
Pérez-Leal, Martín
Estornut, Cristina
Roger, Inés
Pérez-Fidalgo, Alejandro
Sanz, Celia
Cortijo, Julio
author_sort Montero, Paula
collection PubMed
description Paclitaxel is a microtubule-stabilizing chemotherapeutic agent approved for the treatment of ovarian, non-small cell lung, head, neck, and breast cancers. Despite its beneficial effects on cancer and widespread use, paclitaxel also damages healthy tissues, including the skin. However, the mechanisms that drive these skin adverse events are not clearly understood. In the present study, we demonstrated, by using both primary epidermal keratinocytes (NHEK) and a 3D epidermis model, that paclitaxel impairs different cellular processes: paclitaxel increased the release of IL-1α, IL-6, and IL-8 inflammatory cytokines, produced reactive oxygen species (ROS) release and apoptosis, and reduced the endothelial tube formation in the dermal microvascular endothelial cells (HDMEC). Some of the mechanisms driving these adverse skin events in vitro are mediated by the activation of toll-like receptor 4 (TLR-4), which phosphorylate transcription of nuclear factor kappa B (NF-κb). This is the first study analyzing paclitaxel effects on healthy human epidermal cells with an epidermis 3D model, and will help in understanding paclitaxel’s effects on the skin.
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spelling pubmed-88349802022-02-12 Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model Montero, Paula Milara, Javier Pérez-Leal, Martín Estornut, Cristina Roger, Inés Pérez-Fidalgo, Alejandro Sanz, Celia Cortijo, Julio Int J Mol Sci Article Paclitaxel is a microtubule-stabilizing chemotherapeutic agent approved for the treatment of ovarian, non-small cell lung, head, neck, and breast cancers. Despite its beneficial effects on cancer and widespread use, paclitaxel also damages healthy tissues, including the skin. However, the mechanisms that drive these skin adverse events are not clearly understood. In the present study, we demonstrated, by using both primary epidermal keratinocytes (NHEK) and a 3D epidermis model, that paclitaxel impairs different cellular processes: paclitaxel increased the release of IL-1α, IL-6, and IL-8 inflammatory cytokines, produced reactive oxygen species (ROS) release and apoptosis, and reduced the endothelial tube formation in the dermal microvascular endothelial cells (HDMEC). Some of the mechanisms driving these adverse skin events in vitro are mediated by the activation of toll-like receptor 4 (TLR-4), which phosphorylate transcription of nuclear factor kappa B (NF-κb). This is the first study analyzing paclitaxel effects on healthy human epidermal cells with an epidermis 3D model, and will help in understanding paclitaxel’s effects on the skin. MDPI 2022-01-20 /pmc/articles/PMC8834980/ /pubmed/35163066 http://dx.doi.org/10.3390/ijms23031142 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Montero, Paula
Milara, Javier
Pérez-Leal, Martín
Estornut, Cristina
Roger, Inés
Pérez-Fidalgo, Alejandro
Sanz, Celia
Cortijo, Julio
Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model
title Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model
title_full Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model
title_fullStr Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model
title_full_unstemmed Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model
title_short Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model
title_sort paclitaxel-induced epidermal alterations: an in vitro preclinical assessment in primary keratinocytes and in a 3d epidermis model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834980/
https://www.ncbi.nlm.nih.gov/pubmed/35163066
http://dx.doi.org/10.3390/ijms23031142
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