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The toxic effect of cytostatics on primary cilia frequency and multiciliation

A. Filipová, D. Diaz Garcia, A. Bezrouk, D. Čížková, J. Dvořák, S. Filip, J. Sturge, Z. Šinkorová,

. 2019 ; 23 (8) : 5728-5736. [pub] 20190617

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

The primary cilium is considered as a key component of morphological cellular stability. However, cancer cells are notorious for lacking primary cilia in most cases, depending upon the tumour type. Previous reports have shown the effect of starvation and cytostatics on ciliogenesis in normal and cancer cells although with limited success, especially when concerning the latter. In this study, we evaluated the presence and frequency of primary cilia in breast fibroblasts and in triple-negative breast cancer cells after treatment with cytostatics finding that, in the case of breast fibroblasts, primary cilia were detected at their highest incidence 72 hours after treatment with 120 nM doxorubicin. Further, multiciliated cells were also detected after treatment with 80 nM doxorubicin. On the other hand, treatment with taxol increased the number of ciliated cells only at low concentrations (1.25 and 3.25 nM) and did not induce multiciliation. Interestingly, triple-negative breast cancer cells did not present primary cilia after treatment with either doxorubicin or taxol. This is the first study reporting the presence of multiple primary cilia in breast fibroblasts induced by doxorubicin. However, the null effect of these cytostatics on primary cilia incidence in the evaluated triple negative breast carcinomas cell lines requires further research.

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$a Filipová, Alžběta $u Department of Radiobiology, Faculty of Military Health Sciences in Hradec Králové, University of Defence, Hradec Králové, Czech Republic.
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$a The primary cilium is considered as a key component of morphological cellular stability. However, cancer cells are notorious for lacking primary cilia in most cases, depending upon the tumour type. Previous reports have shown the effect of starvation and cytostatics on ciliogenesis in normal and cancer cells although with limited success, especially when concerning the latter. In this study, we evaluated the presence and frequency of primary cilia in breast fibroblasts and in triple-negative breast cancer cells after treatment with cytostatics finding that, in the case of breast fibroblasts, primary cilia were detected at their highest incidence 72 hours after treatment with 120 nM doxorubicin. Further, multiciliated cells were also detected after treatment with 80 nM doxorubicin. On the other hand, treatment with taxol increased the number of ciliated cells only at low concentrations (1.25 and 3.25 nM) and did not induce multiciliation. Interestingly, triple-negative breast cancer cells did not present primary cilia after treatment with either doxorubicin or taxol. This is the first study reporting the presence of multiple primary cilia in breast fibroblasts induced by doxorubicin. However, the null effect of these cytostatics on primary cilia incidence in the evaluated triple negative breast carcinomas cell lines requires further research.
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$a Díaz Garcia, Daniel $u Department of Clinical Biochemistry and Diagnostics, University Hospital, Hradec Králové, Czech Republic. $7 xx0318858
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$a Bezrouk, Aleš $u Department of Medical Biophysics, Faculty of Medicine, Charles University, Hradec Králové, Czech Republic.
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$a Čížková, Dana $u Department of Histology and Embryology, Faculty of Medicine, Charles University, Hradec Králové, Czech Republic.
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$a Dvořák, Josef $u Department of Oncology, Thomayer Hospital, Charles University, Prague, Czech Republic.
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$a Filip, Stanislav $u Department of Oncology and Radiotherapy, Faculty of Medicine, Charles University, Hradec Králové, Czech Republic.
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$a Sturge, Justin $u Department of Biomedical Sciences, Faculty of Health Sciences, University of Hull, Hull, UK.
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