Doxorubicin Assisted by Microsecond Electroporation Promotes Irreparable Morphological Alternations in Sensitive and Resistant Human Breast Adenocarcinoma Cells

Rembiałkowska, Nina; Dubińska–Magiera, Magda; Sikora, Andrzej; Szlasa, Wojciech; Szewczyk, Anna; Czapor-Irzabek, Hanna; Daczewska, Małgorzata; Saczko, Jolanta; Kulbacka, Julita

doi:10.3390/app10082765

Cited by 20 publications

(21 citation statements)

References 52 publications

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“…Thus, any change in the actin’s organization would result in altered resistance of the cell towards lateral membrane expansion. PEF treatment influences the cell’s shape as recently reviewed by Kotnik et al [ 2 ] and critical changes in the morphology of the cells are induced following electroporation as reported by Rembiałkowska et al [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

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Atorvastatin Modulates the Efficacy of Electroporation and Calcium Electrochemotherapy

Szlasa

Szewczyk

Novickij

et al. 2021

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

“…Most of the research aiming to increase the efficiency of ECT concerns optimization of the electroporation’s protocols [ 6 , 11 , 12 , 13 , 14 , 15 ]. Alternatively, enhancing the effect of CaEP might be achieved by modifications of the physical properties of the targeted cells to make them more susceptible to EP.…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin Modulates the Efficacy of Electroporation and Calcium Electrochemotherapy

Szlasa

Szewczyk

Novickij

et al. 2021

IJMS

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“…In this technique, called often, therefore, electroporation, when low-voltage pulses are applied, the increased permeability of the cell membranes is transient, and after a definite time lapse, the cells recover their integrity. During this time lapse, the inflow of compounds to the cytoplasm may take place, which is used today as an effective way for drug or gene delivery [ 31 , 32 ]. In contrast, when rather high-voltage pulses are applied, the membranes might be permanently damaged, in which case, the concerned cells undergo necrosis [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Oxidative Effects during Irreversible Electroporation of Melanoma Cells—In Vitro Study

et al. 2020

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Irreversible electroporation (IRE) is today used as an alternative to surgery for the excision of cancer lesions. This study aimed to investigate the oxidative and cytotoxic effects the cells undergo during irreversible electroporation using IRE protocols. To do so, we used IRE-inducing pulsed electric fields (PEFs) (eight pulses of 0.1 ms duration and 2–4 kV/cm intensity) and compared their effects to those of PEFs of intensities below the electroporation threshold (eight pulses, 0.1 ms, 0.2–0.4 kV/cm) and the PEFs involving elongated pulses (eight pulses, 10 ms, 0.2–0.4 kV/cm). Next, to follow the morphology of the melanoma cell membranes after treatment with the PEFs, we analyzed the permeability and integrity of their membranes and analyzed the radical oxygen species (ROS) bursts and the membrane lipids’ oxidation. Our data showed that IRE-induced high cytotoxic effect is associated both with irreversible cell membrane disruption and ROS-associated oxidation, which is occurrent also in the low electric field range. It was shown that the viability of melanoma cells characterized by similar ROS content and lipid membrane oxidation after PEF treatment depends on the integrity of the membrane system. Namely, when the effects of the PEF on the membrane are reversible, aside from the high level of ROS and membrane oxidation, the cell does not undergo cell death.

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“…The therapeutic efficacy of chemotherapy in many types of tumors is dramatically hindered by multidrug resistance (MDR). Our previous study, where ESOPE-based protocols with DOX or other drugs were used, indicated a promising usage in colon cancer [ 13 , 14 ], gastric [ 15 ], and breast cancer cells [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Micro- and Nanosecond Pulses Used in Doxorubicin Electrochemotherapy in Human Breast and Colon Cancer Cells with Drug Resistance

et al. 2022

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(1) Background: Pulsed electric field (PEF) techniques are commonly used to support the delivery of various molecules. A PEF seems a promising method for low permeability drugs or when cells demonstrate therapy resistance and the cell membrane becomes an impermeable barrier. (2) Methods: In this study, we have used doxorubicin-resistant and sensitive models of human breast cancer (MCF-7/DX, MCF-7/WT) and colon cancer cells (LoVo, LoVoDX). The study aimed to investigate the susceptibility of the cells to doxorubicin (DOX) and electric fields in the 20–900 ns pulse duration range. The viability assay was utilized to evaluate the PEF protocols’ efficacy. Cell confluency and reduced glutathione were measured after PEF protocols. (3) Results: The obtained results showed that PEFs significantly supported doxorubicin delivery and cytotoxicity after 48 and 72 h. The 60 kV/cm ultrashort pulses × 20 ns × 400 had the most significant cytotoxic anticancer effect. The increase in DOX concentration provokes a decrease in cell viability, affected cell confluency, and reduced GSSH when combined with the ESOPE (European Standard Operating Procedures of Electrochemotherapy) protocol. Additionally, reactive oxygen species after PEF and PEF-DOX were detected. (4) Conclusions: Ultrashort electric pulses with low DOX content or ESOPE with higher DOX content seem the most promising in colon and breast cancer treatment.

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Doxorubicin Assisted by Microsecond Electroporation Promotes Irreparable Morphological Alternations in Sensitive and Resistant Human Breast Adenocarcinoma Cells

Cited by 20 publications

References 52 publications

Atorvastatin Modulates the Efficacy of Electroporation and Calcium Electrochemotherapy

Atorvastatin Modulates the Efficacy of Electroporation and Calcium Electrochemotherapy

Oxidative Effects during Irreversible Electroporation of Melanoma Cells—In Vitro Study

Micro- and Nanosecond Pulses Used in Doxorubicin Electrochemotherapy in Human Breast and Colon Cancer Cells with Drug Resistance

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