In Vitro Study of Calcium Microsecond Electroporation of Prostate Adenocarcinoma Cells

Szlasa, Wojciech; Michel, Olga; Szewczyk, Anna; Tarek, Mounir; Saczko, Jolanta; Kulbacka, Julita

doi:10.3390/molecules25225406

Cited by 15 publications

(12 citation statements)

References 73 publications

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“…In several previous studies, we showed that the reorganization of actin has a significant effect on the therapeutic outcome of the therapy of melanoma and prostate cancer cells and thus can be used as a target for the anti-cancer therapy [ 47 ]. We also showed that CaEP highly affects prostate cancer cells’ actin cytoskeleton [ 3 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Electroporation (EP) refers to the phenomenon describing the permeabilization of cell membranes subjected to the electric fields of intensity well above a threshold, believed to result from the formation of pores. Such pores allow the release or intracellular material or the uptake of drugs or genetic material by the cells [ 1 , 2 , 3 ] in electroporation-based technologies and treatments. In clinical setups where electroporation is combined with chemotherapeutics, the method is known as electrochemotherapy (ECT), and calcium electroporation (CaEP) is a specific subset in which calcium ions are the substance to deliver to treated cells.…”

Section: Introductionmentioning

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%

Section: Introductionmentioning

confidence: 99%

Atorvastatin Modulates the Efficacy of Electroporation and Calcium Electrochemotherapy

Szlasa

Szewczyk

Novickij

et al. 2021

IJMS

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“…The applied method does not prevent the cells' sedimentation and their random rotation, affecting the sensitization 33 . Recently we proved that calcium ions could enhance the cytotoxicity of microsecond electroporation of prostate adenocarcinoma cells 34 . This study confirms that a burst of high-frequency nsPEFs with the presence of the extracellular Ca 2+ also triggers extensive cell death.…”

Section: Discussionmentioning

confidence: 99%

Effects of high-frequency nanosecond pulses on prostate cancer cells

Szlasa

Novickij

Szewczyk

et al. 2021

Sci Rep

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Electroporation with pulsed electric fields show a potential to be applied as an experimental focal therapy of tumors. Sub-microsecond regime of electric pulses displays unique electrophysical features operative in cells and membranes. Recently, MHz compression of nanosecond pulses electric fields (nsPEFs) bursts proved to enhance the effectiveness of the therapy. High morbidity of prostate cancer (PCa) and risk of overtreatment associated with this malignancy call for new minimal-invasive treatment alternative. Herein we present the in vitro study for developing applications based on this new technology. In this study, we used flow cytometric analysis, cell viability assay, caspase activity analysis, wound healing assay, confocal microscopy study, and immunofluorescence to investigate the biological effect of high-frequency nsPEFs on PCa cells. Our results show that high-frequency nsPEFs induces the permeabilization and cell death of PCa cells. The cytotoxicity is significantly enhanced in MHz compression of pulses and with the presence of extracellular Ca2+. High-frequency nsPEFs trigger changes in PCa cells’ cytoskeleton and their mobility. The presented data show a therapeutic potential of high-frequency nsPEFs in a PCa setting. The sub-microsecond regime of pulses can potentially be applied in nanosecond electroporation protocols for PCa treatment.

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“…40 Activation of calcium signaling has been widely evaluated for its potential application in the activation of the intrinsic apoptotic pathway in cancer. 41 The assumption is that activation of calcium inflow to the cytoplasm and the mitochondria would result in programmed cell death. However, in the case of TRPV1, the effect varies between analyzed cell lines and, curiously, is related to the level of TRPV1 expression.…”

Section: Trpv1mentioning

confidence: 99%

Therapeutic role of vanillin receptors in cancer

Rakoczy¹,

Szlasa²,

Saczko³

et al. 2021

Adv Clin Exp Med

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Natural products play significant roles in the development of novel drugs. One of such compounds is vanillin -a natural substance commonly used in food. Anticancer potential of the substance is continually encouraging researchers to conduct further investigations. A rising number of publications describe the role of 4-hydroxy-3-methoxybenzaldehyde (vanillin) in the process of inhibiting tumor growth. Four vanilloid receptors play significant roles in the response of cancer cells to the natural compound. Each of these proteins can be individually affected by vanillin; thus, the substance either leads to inhibition of the cell proliferation or increases the Ca 2+ level. The TRPV1, a non-selective cation channel permeable to calcium, acts on cancer development and progression. Thus, vanilloid receptors have the potential to become the target for therapeutical research. Moreover, selective inhibitors of the receptor have proved their efficacy in vitro. CK2α is an antiapoptotic, cancer-sustaining protein and, therefore, the inhibitor of apoptosis. Thus, drugs that exhibit allosteric and ATP-competitive inhibition of the protein might be crucial for cancer therapy. CAMK4 is a protein kinase expression associated with a wide array of cancers. Also, MARK4 is another kinase responsible for the stability of microtubules, overexpressed in many cancer types. Studies concerning this protein revealed that microtubule impairment might be a cancer therapy direction. This review aims to demonstrate the crucial role of described vanilloid receptors in inhibiting the proliferation of cancer cells and to prove the usefulness of using vanillin and its derivatives in the process of drug design.

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In Vitro Study of Calcium Microsecond Electroporation of Prostate Adenocarcinoma Cells

Cited by 15 publications

References 73 publications

Atorvastatin Modulates the Efficacy of Electroporation and Calcium Electrochemotherapy

Atorvastatin Modulates the Efficacy of Electroporation and Calcium Electrochemotherapy

Effects of high-frequency nanosecond pulses on prostate cancer cells

Therapeutic role of vanillin receptors in cancer

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