Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity

Wafaa Al-Tameemi, Christopher Dunnill, Omar Hussain, Manon M. Komen, Corina J. van den Hurk, Andrew Collett, Nikolaos T. Georgopoulos

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

A highly distressing side-effect of cancer chemotherapy is chemotherapy-induced alopecia (CIA). Scalp cooling remains the only treatment for CIA, yet there is no experimental evidence to support the cytoprotective capacity of cooling. We have established a series of in vitro models for the culture of human keratinocytes under conditions where they adopt a basal, highly-proliferative phenotype thus resembling the rapidly-dividing sub-population of native hair-matrix keratinocytes. Using a panel of chemotherapy drugs routinely used clinically (docetaxel, doxorubicin and the active metabolite of cyclophosphamide 4-OH-CP), we demonstrate that although these drugs are highly-cytotoxic, cooling can markedly reduce or completely inhibit drug cytotoxicity, in agreement with clinical observations. By contrast, we show that cytotoxicity caused by specific combinatorial drug treatments cannot be adequately attenuated by cooling, supporting data showing that such treatments do not always respond well to cooling clinically. Importantly, we provide evidence that the choice of temperature may be critical in determining the efficacy of cooling in rescuing cells from drug-mediated toxicity. Therefore, despite their reductive nature, these in vitro models have provided experimental evidence for the clinically-reported cytoprotective role of cooling and represent useful tools for future studies on the molecular mechanisms of cooling-mediated cytoprotection.

LanguageEnglish
Pages1366-1376
Number of pages11
JournalToxicology in Vitro
Volume28
Issue number8
DOIs
Publication statusPublished - 2014

Fingerprint

Chemotherapy
Cytotoxicity
Keratinocytes
Cooling
Drug Therapy
Alopecia
docetaxel
Pharmaceutical Preparations
Cytoprotection
Scalp
Drug-Related Side Effects and Adverse Reactions
Hair
Doxorubicin
Cyclophosphamide
Therapeutics
Phenotype
Drug therapy
Temperature
In Vitro Techniques
Metabolites

Cite this

@article{c442e257858a48b78a82d076f50ff99f,
title = "Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity",
abstract = "A highly distressing side-effect of cancer chemotherapy is chemotherapy-induced alopecia (CIA). Scalp cooling remains the only treatment for CIA, yet there is no experimental evidence to support the cytoprotective capacity of cooling. We have established a series of in vitro models for the culture of human keratinocytes under conditions where they adopt a basal, highly-proliferative phenotype thus resembling the rapidly-dividing sub-population of native hair-matrix keratinocytes. Using a panel of chemotherapy drugs routinely used clinically (docetaxel, doxorubicin and the active metabolite of cyclophosphamide 4-OH-CP), we demonstrate that although these drugs are highly-cytotoxic, cooling can markedly reduce or completely inhibit drug cytotoxicity, in agreement with clinical observations. By contrast, we show that cytotoxicity caused by specific combinatorial drug treatments cannot be adequately attenuated by cooling, supporting data showing that such treatments do not always respond well to cooling clinically. Importantly, we provide evidence that the choice of temperature may be critical in determining the efficacy of cooling in rescuing cells from drug-mediated toxicity. Therefore, despite their reductive nature, these in vitro models have provided experimental evidence for the clinically-reported cytoprotective role of cooling and represent useful tools for future studies on the molecular mechanisms of cooling-mediated cytoprotection.",
keywords = "Chemotherapy, Cooling, Cytoprotection, Cytotoxicity, Keratinocytes",
author = "Wafaa Al-Tameemi and Christopher Dunnill and Omar Hussain and Komen, {Manon M.} and {van den Hurk}, {Corina J.} and Andrew Collett and Georgopoulos, {Nikolaos T.}",
year = "2014",
doi = "10.1016/j.tiv.2014.07.011",
language = "English",
volume = "28",
pages = "1366--1376",
journal = "Toxicology in Vitro",
issn = "0887-2333",
publisher = "Elsevier Limited",
number = "8",

}

Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity. / Al-Tameemi, Wafaa; Dunnill, Christopher; Hussain, Omar; Komen, Manon M.; van den Hurk, Corina J.; Collett, Andrew; Georgopoulos, Nikolaos T.

In: Toxicology in Vitro, Vol. 28, No. 8, 2014, p. 1366-1376.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Use of in vitro human keratinocyte models to study the effect of cooling on chemotherapy drug-induced cytotoxicity

AU - Al-Tameemi, Wafaa

AU - Dunnill, Christopher

AU - Hussain, Omar

AU - Komen, Manon M.

AU - van den Hurk, Corina J.

AU - Collett, Andrew

AU - Georgopoulos, Nikolaos T.

PY - 2014

Y1 - 2014

N2 - A highly distressing side-effect of cancer chemotherapy is chemotherapy-induced alopecia (CIA). Scalp cooling remains the only treatment for CIA, yet there is no experimental evidence to support the cytoprotective capacity of cooling. We have established a series of in vitro models for the culture of human keratinocytes under conditions where they adopt a basal, highly-proliferative phenotype thus resembling the rapidly-dividing sub-population of native hair-matrix keratinocytes. Using a panel of chemotherapy drugs routinely used clinically (docetaxel, doxorubicin and the active metabolite of cyclophosphamide 4-OH-CP), we demonstrate that although these drugs are highly-cytotoxic, cooling can markedly reduce or completely inhibit drug cytotoxicity, in agreement with clinical observations. By contrast, we show that cytotoxicity caused by specific combinatorial drug treatments cannot be adequately attenuated by cooling, supporting data showing that such treatments do not always respond well to cooling clinically. Importantly, we provide evidence that the choice of temperature may be critical in determining the efficacy of cooling in rescuing cells from drug-mediated toxicity. Therefore, despite their reductive nature, these in vitro models have provided experimental evidence for the clinically-reported cytoprotective role of cooling and represent useful tools for future studies on the molecular mechanisms of cooling-mediated cytoprotection.

AB - A highly distressing side-effect of cancer chemotherapy is chemotherapy-induced alopecia (CIA). Scalp cooling remains the only treatment for CIA, yet there is no experimental evidence to support the cytoprotective capacity of cooling. We have established a series of in vitro models for the culture of human keratinocytes under conditions where they adopt a basal, highly-proliferative phenotype thus resembling the rapidly-dividing sub-population of native hair-matrix keratinocytes. Using a panel of chemotherapy drugs routinely used clinically (docetaxel, doxorubicin and the active metabolite of cyclophosphamide 4-OH-CP), we demonstrate that although these drugs are highly-cytotoxic, cooling can markedly reduce or completely inhibit drug cytotoxicity, in agreement with clinical observations. By contrast, we show that cytotoxicity caused by specific combinatorial drug treatments cannot be adequately attenuated by cooling, supporting data showing that such treatments do not always respond well to cooling clinically. Importantly, we provide evidence that the choice of temperature may be critical in determining the efficacy of cooling in rescuing cells from drug-mediated toxicity. Therefore, despite their reductive nature, these in vitro models have provided experimental evidence for the clinically-reported cytoprotective role of cooling and represent useful tools for future studies on the molecular mechanisms of cooling-mediated cytoprotection.

KW - Chemotherapy

KW - Cooling

KW - Cytoprotection

KW - Cytotoxicity

KW - Keratinocytes

UR - http://www.scopus.com/inward/record.url?scp=84905916573&partnerID=8YFLogxK

U2 - 10.1016/j.tiv.2014.07.011

DO - 10.1016/j.tiv.2014.07.011

M3 - Article

VL - 28

SP - 1366

EP - 1376

JO - Toxicology in Vitro

T2 - Toxicology in Vitro

JF - Toxicology in Vitro

SN - 0887-2333

IS - 8

ER -