Wafaa Al-Tameemi1, Christopher Dunnill1, Omar Hussain2, Manon M Komen3, Corina J van den Hurk4, Andrew Collett1, Nikolaos T Georgopoulos5
1Department of Biological Sciences, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK.
2Department of Biological Sciences, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK; Paxman Coolers, International House, Fenay Bridge, Huddersfield, UK.
3Department of Internal Medicine and Medical Oncology, Medical Centre Alkmaar, Alkmaar, The Netherlands.
4Research Department, Eindhoven Cancer Registry/Comprehensive Cancer Centre South, Eindhoven, The Netherlands.
5Department of Biological Sciences, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK. Electronic address: N.Georgopoulos@hud.ac.uk.
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.
Chemotherapy; Cooling; Cytoprotection; Cytotoxicity; Keratinocytes.
Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.
