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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Electroporation is influenced by the features of the targeted cell membranes, e.g., the cholesterol content and the surface tension of the membrane. The latter is eventually affected by the organization of actin fibers. Atorvastatin is a statin known to influence both the cholesterol content and the organization of actin. This work analyzes the effects of the latter on the efficacy of electroporation of cancer cells. In addition, herein, electroporation was combined with calcium chloride (CaEP) to assess as well the effects of the statin on the efficacy of electrochemotherapy. Cholesterol-rich cell lines MDA-MB231, DU 145, and A375 underwent (1) 48 h preincubation or (2) direct treatment with 50 nM atorvastatin. We studied the impact of the statin on cholesterol and actin fiber organization and analyzed the cells’ membrane permeability. The viability of cells subjected to PEF (pulsed electric field) treatments and CaEP with 5 mM CaCl2 was examined. Finally, to assess the safety of the therapy, we analyzed the N-and E-cadherin localization using confocal laser microscopy. The results of our investigation revealed that depending on the cell line, atorvastatin preincubation decreases the total cholesterol in the steroidogenic cells and induces reorganization of actin nearby the cell membrane. Under low voltage PEFs, actin reorganization is responsible for the increase in the electroporation threshold. However, when subject to high voltage PEF, the lipid composition of the cell membrane becomes the regulatory factor. Namely, preincubation with atorvastatin reduces the cytotoxic effect of low voltage pulses and enhances the cytotoxicity and cellular changes induced by high voltage pulses. The study confirms that the surface tension regulates of membrane permeability under low voltage PEF treatment. Accordingly, to reduce the unfavorable effects of preincubation with atorvastatin, electroporation of steroidogenic cells should be performed at high voltage and combined with a calcium supply.

Details

Title
Atorvastatin Modulates the Efficacy of Electroporation and Calcium Electrochemotherapy
Author
Szlasa, Wojciech 1   VIAFID ORCID Logo  ; Kiełbik, Aleksander 2   VIAFID ORCID Logo  ; Szewczyk, Anna 3 ; Novickij, Vitalij 4 ; Mounir Tarek 5   VIAFID ORCID Logo  ; Łapińska, Zofia 6 ; Saczko, Jolanta 6   VIAFID ORCID Logo  ; Kulbacka, Julita 6   VIAFID ORCID Logo  ; Rembiałkowska, Nina 6 

 Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland; [email protected] 
 Medical University Hospital, 50-556 Wroclaw, Poland; [email protected]; Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland; [email protected] (A.S.); [email protected] (Z.Ł.); [email protected] (J.S.); [email protected] (J.K.) 
 Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland; [email protected] (A.S.); [email protected] (Z.Ł.); [email protected] (J.S.); [email protected] (J.K.); Department of Animal Developmental Biology, Institute of Experimental Biology, University of Wroclaw, 50-335 Wroclaw, Poland 
 Institute of High Magnetic Fields, Vilnius Gediminas Technical University, 03227 Vilnius, Lithuania; [email protected] 
 Université de Lorraine, CNRS, LPCT, F-54000 Nancy, France; [email protected] 
 Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland; [email protected] (A.S.); [email protected] (Z.Ł.); [email protected] (J.S.); [email protected] (J.K.) 
First page
11245
Publication year
2021
Publication date
2021
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2584438571
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.