The Impact of Extracellular Ca<sup>2+</sup> and Nanosecond Electric Pulses on Sensitive and Drug-Resistant Human Breast and Colon Cancer Cells

(1) Background: Calcium electroporation (CaEP) is based on the application of electrical pulses to permeabilize cells (electroporation) and allow cytotoxic doses of calcium to enter the cell. (2) Methods: In this work, we have used doxorubicin-resistant (DX) and non-resistant models of human breast...

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Main Authors: Julita Kulbacka, Nina Rembiałkowska, Anna Szewczyk, Helena Moreira, Anna Szyjka, Irutė Girkontaitė, Kamil P. Grela, Vitalij Novickij
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/13/3216
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author Julita Kulbacka
Nina Rembiałkowska
Anna Szewczyk
Helena Moreira
Anna Szyjka
Irutė Girkontaitė
Kamil P. Grela
Vitalij Novickij
author_facet Julita Kulbacka
Nina Rembiałkowska
Anna Szewczyk
Helena Moreira
Anna Szyjka
Irutė Girkontaitė
Kamil P. Grela
Vitalij Novickij
author_sort Julita Kulbacka
collection DOAJ
description (1) Background: Calcium electroporation (CaEP) is based on the application of electrical pulses to permeabilize cells (electroporation) and allow cytotoxic doses of calcium to enter the cell. (2) Methods: In this work, we have used doxorubicin-resistant (DX) and non-resistant models of human breast cancer (MCF-7/DX, MCF-7/WT) and colon cancer cells (LoVo, LoVo/DX), and investigated the susceptibility of the cells to extracellular Ca<sup>2+</sup> and electric fields in the 20 ns–900 ns pulse duration range. (3) Results: We have observed that colon cancer cells were less susceptible to PEF than breast cancer cells. An extracellular Ca<sup>2+</sup> (2 mM) with PEF was more disruptive for DX-resistant cells. The expression of glycoprotein P (MDR1, P-gp) as a drug resistance marker was detected by the immunofluorescent (CLSM) method and rhodamine-123 efflux as an MDR1 activity. MDR1 expression was not significantly modified by nanosecond electroporation in multidrug-resistant cells, but a combination with calcium ions significantly inhibited MDR1 activity and cell viability. (4) Conclusions: We believe that PEF with calcium ions can reduce drug resistance by inhibiting drug efflux activity. This phenomenon of MDR mechanism disruption seems promising in anticancer protocols.
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spelling doaj.art-f240961028a2489bb273c8581f29b9962023-11-22T01:59:28ZengMDPI AGCancers2072-66942021-06-011313321610.3390/cancers13133216The Impact of Extracellular Ca<sup>2+</sup> and Nanosecond Electric Pulses on Sensitive and Drug-Resistant Human Breast and Colon Cancer CellsJulita Kulbacka0Nina Rembiałkowska1Anna Szewczyk2Helena Moreira3Anna Szyjka4Irutė Girkontaitė5Kamil P. Grela6Vitalij Novickij7Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, 50-367 Wroclaw, PolandDepartment of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, 50-367 Wroclaw, PolandDepartment of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, 50-367 Wroclaw, PolandDepartment of Basic Medical Science, Faculty of Pharmacy, Wroclaw Medical University, 50-367 Wroclaw, PolandDepartment of Basic Medical Science, Faculty of Pharmacy, Wroclaw Medical University, 50-367 Wroclaw, PolandDepartment of Immunology, State Research Institute Centre for Innovative Medicine, 08406 Vilnius, LithuaniaDepartment of Drugs Form Technology, Faculty of Pharmacy, Wroclaw Medical University, 50-367 Wroclaw, PolandInstitute of High Magnetic Fields, Vilnius Gediminas Technical University, 10223 Vilnius, Lithuania(1) Background: Calcium electroporation (CaEP) is based on the application of electrical pulses to permeabilize cells (electroporation) and allow cytotoxic doses of calcium to enter the cell. (2) Methods: In this work, we have used doxorubicin-resistant (DX) and non-resistant models of human breast cancer (MCF-7/DX, MCF-7/WT) and colon cancer cells (LoVo, LoVo/DX), and investigated the susceptibility of the cells to extracellular Ca<sup>2+</sup> and electric fields in the 20 ns–900 ns pulse duration range. (3) Results: We have observed that colon cancer cells were less susceptible to PEF than breast cancer cells. An extracellular Ca<sup>2+</sup> (2 mM) with PEF was more disruptive for DX-resistant cells. The expression of glycoprotein P (MDR1, P-gp) as a drug resistance marker was detected by the immunofluorescent (CLSM) method and rhodamine-123 efflux as an MDR1 activity. MDR1 expression was not significantly modified by nanosecond electroporation in multidrug-resistant cells, but a combination with calcium ions significantly inhibited MDR1 activity and cell viability. (4) Conclusions: We believe that PEF with calcium ions can reduce drug resistance by inhibiting drug efflux activity. This phenomenon of MDR mechanism disruption seems promising in anticancer protocols.https://www.mdpi.com/2072-6694/13/13/3216calcium ionselectroporation drug resistancehuman adenocarcinomamembrane permeabilization
spellingShingle Julita Kulbacka
Nina Rembiałkowska
Anna Szewczyk
Helena Moreira
Anna Szyjka
Irutė Girkontaitė
Kamil P. Grela
Vitalij Novickij
The Impact of Extracellular Ca<sup>2+</sup> and Nanosecond Electric Pulses on Sensitive and Drug-Resistant Human Breast and Colon Cancer Cells
Cancers
calcium ions
electroporation drug resistance
human adenocarcinoma
membrane permeabilization
title The Impact of Extracellular Ca<sup>2+</sup> and Nanosecond Electric Pulses on Sensitive and Drug-Resistant Human Breast and Colon Cancer Cells
title_full The Impact of Extracellular Ca<sup>2+</sup> and Nanosecond Electric Pulses on Sensitive and Drug-Resistant Human Breast and Colon Cancer Cells
title_fullStr The Impact of Extracellular Ca<sup>2+</sup> and Nanosecond Electric Pulses on Sensitive and Drug-Resistant Human Breast and Colon Cancer Cells
title_full_unstemmed The Impact of Extracellular Ca<sup>2+</sup> and Nanosecond Electric Pulses on Sensitive and Drug-Resistant Human Breast and Colon Cancer Cells
title_short The Impact of Extracellular Ca<sup>2+</sup> and Nanosecond Electric Pulses on Sensitive and Drug-Resistant Human Breast and Colon Cancer Cells
title_sort impact of extracellular ca sup 2 sup and nanosecond electric pulses on sensitive and drug resistant human breast and colon cancer cells
topic calcium ions
electroporation drug resistance
human adenocarcinoma
membrane permeabilization
url https://www.mdpi.com/2072-6694/13/13/3216
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