Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model
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Other documents of the author: Sanz, Celia; Montero, Paula; MILARA, JAVIER; Pérez-Leal, Martín; Estornut, Cristina; Roger, Inés; Pérez-Fidalgo, J. Alejandro; Cortijo, Julio
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Title
Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis ModelAuthor (s)
Date
2022-01-22Publisher
MDPIBibliographic citation
Montero, P.; Milara, J.; Pérez-Leal, M.; Estornut, C.; Roger, I.; Pérez-Fidalgo, A.; Sanz, C.; Cortijo, J. Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model. Int. J. Mol. Sci. 2022, 23, 1142. https:// doi.org/10.3390/ijms23031142Type
info:eu-repo/semantics/articlePublisher version
https://www.mdpi.com/1422-0067/23/3/1142Version
info:eu-repo/semantics/publishedVersionSubject
Abstract
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 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. [-]
Is part of
International Journal of Molecular Sciences. 2022, 23 (3), 1142. https://doi.org/10.3390/ijms23031142Funder Name
Fondo Europeo de Desarrollo Regional (FEDER) | Instituto de Salud Carlos III | Gobierno de España | Generalitat Valenciana
Project code
PID2020-114871RB-I00 | PI20/01363 | CB06/06/0027 | 2017/023/UV
Project title or grant
CIBERES | Regional Government Prometeo
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© 2022 by the authors
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