Cooling-mediated protection from chemotherapy drug-induced cytotoxicity in human keratinocytes by inhibition of cellular drug uptake

Autor: Megan A Palmer, Khalidah Ibraheem, Myria Ioannou, Andrew Collett, Michael Peake, Christopher Dunnill, Nikolaos T. Georgopoulos, Adrian Smith
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Keratinocytes
medicine.medical_treatment
Cytotoxicity
Cancer Treatment
Toxicology
Pathology and Laboratory Medicine
Epithelium
0302 clinical medicine
Spectrum Analysis Techniques
Animal Cells
Medicine and Health Sciences
Cells
Cultured
Multidisciplinary
Antibiotics
Antineoplastic
medicine.diagnostic_test
Chemistry
Pharmaceutics
Flow Cytometry
Cytoprotection
Cold Temperature
Oncology
Spectrophotometry
030220 oncology & carcinogenesis
Medicine
Cytophotometry
Cellular Types
Anatomy
Hair Follicle
medicine.drug
Epirubicin
Research Article
Clinical Oncology
Cell Physiology
Science
Research and Analysis Methods
Flow cytometry
03 medical and health sciences
Cancer Chemotherapy
Drug Therapy
medicine
Chemotherapy
Humans
Doxorubicin
Scalp
Cancer
Biology and Life Sciences
Epithelial Cells
Cell Biology
medicine.disease
In vitro
030104 developmental biology
Biological Tissue
Cancer research
Cytotoxic Chemotherapy
Clinical Medicine
Cell Immortalization
Head
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 10, p e0240454 (2020)
ISSN: 1932-6203
Popis: Chemotherapy-induced alopecia (CIA) represents the most distressing side-effect for cancer patients. Scalp cooling is currently the only treatment to combat CIA, yet little is known about its cytoprotective effects in human hair follicles (HF). We have previously established in vitro human keratinocyte models to study the effects of taxanes and anthracyclines routinely-used clinically and reported that cooling markedly-reduced or even completely-prevented cytotoxicity in a temperature dependent manner. Using these models (including HF-derived primary keratinocytes), we now demonstrate that cooling markedly attenuates cellular uptake of the anthracyclines doxorubicin and epirubicin to reduce or prevent drug-mediated human keratinocyte cytotoxicity. We show marked reduction in drug uptake and nuclear localization qualitatively by fluorescence microscopy. We have also devised a flow cytometry-based methodology that permitted semi-quantitative analysis of differences in drug uptake, which demonstrated that cooling can reduce drug uptake by up to ~8-fold in comparison to normal/physiological temperature, an effect that was temperature-dependent. Our results provide evidence that attenuation of cellular drug uptake represents at least one of the mechanisms underpinning the ability of cooling to rescue human keratinocytes from chemotherapy drug-cytotoxicity, thus supporting the clinical efficacy of scalp cooling.
Databáze: OpenAIRE
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