Calcium electroporation causes ATP depletion in cells and is effective both in microsecond and nanosecond pulse range as a modality of electrochemotherapy

Radzevičiūtė-Valčiukė, Eivina; Malyško-Ptašinskė, Veronika; Mickevičiūtė, Eglė; Kulbacka, Julita; Rembiałkowska, Nina; Zinkevičienė, Auksė; Novickij, Jurij; Novickij, Vitalij

doi:10.1016/j.bioelechem.2023.108574

Cited by 3 publications

(1 citation statement)

References 42 publications

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“…ATP was released immediately after HI-PEMF treatment and afterwards started to decrease and remained low (same level as control) for the next 24 h. Biological cells deplete intracellular ATP or release it into extracellular space either under basal conditions or in response to stress or certain stimuli [63,64], which include oxidative and mechanical stimuli or membrane damage in the case of electroporation. Acute depletion or release of ATP during irreversible [65] and reversible electroporation [38,66,67] have been reported, indicating dose-dependent damage-associated molecular patterns following pulsed electric field treatment, which may have an effect on local inflammatory responses and possibilities for immunomodulation [68]. Therefore, we believe that ATP release in HI-PEMF is passive (i.e., driven by concentration gradient) and occurs due to a transient increase in cell membrane permeability.…”

Section: Discussionmentioning

confidence: 87%

Determination of the Impact of High-Intensity Pulsed Electromagnetic Fields on the Release of Damage-Associated Molecular Pattern Molecules

Kranjc,

Polajžer,

Novickij

et al. 2023

IJMS

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High-Intensity Pulsed Electromagnetic Fields (HI-PEMF) treatment is an emerging noninvasive and contactless alternative to conventional electroporation, since the electric field inside the tissue is induced remotely by an externally applied pulsed magnetic field. Recently, HI-PEMF has been successfully used in the transfer of plasmid DNA and siRNA in vivo, with no or minimal infiltration of immune cells. In addition to gene electrotransfer, treatment with HI-PEMF has also shown potential for electrochemotherapy, where activation of the immune response contributes to the treatment outcome. The immune response can be triggered by immunogenic cell death that is characterized by the release of damage-associated molecular patterns (DAMPs) from damaged or/and dying cells. In this study, the release of the best-known DAMP molecules, i.e., adenosine triphosphate (ATP), calreticulin and high mobility group box 1 protein (HMBG1), after HI-PEMF treatment was investigated in vitro on three different cell lines of different tissue origin and compared with conventional electroporation treatment parameters. We have shown that HI-PEMF by itself does not cause the release of HMGB1 or calreticulin, whereas the release of ATP was detected immediately after HI-PEMF treatment. Our results indicate that HI-PEMF treatment causes no to minimal release of DAMP molecules, which results in minimal/limited activation of the immune response.

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Section: Discussionmentioning

confidence: 87%

Determination of the Impact of High-Intensity Pulsed Electromagnetic Fields on the Release of Damage-Associated Molecular Pattern Molecules

Kranjc,

Polajžer,

Novickij

et al. 2023

IJMS

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Mitochondrial depolarization and ATP loss during high frequency nanosecond and microsecond electroporation

Malakauskaitė,

Želvys,

Zinkevičienė

et al. 2024

Bioelectrochemistry

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Electrochemotherapy for head and neck cancers: possibilities and limitations

Morozas,

Malyško-Ptašinskė,

Kulbacka

et al. 2024

Front. Oncol.

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Head and neck cancer continues to be among the most prevalent types of cancer globally, yet it can be managed with appropriate treatment approaches. Presently, chemotherapy and radiotherapy stand as the primary treatment modalities for various groups and regions affected by head and neck cancer. Nonetheless, these treatments are linked to adverse side effects in patients. Moreover, due to tumor resistance to multiple drugs (both intrinsic and extrinsic) and radiotherapy, along with numerous other factors, recurrences or metastases often occur. Electrochemotherapy (ECT) emerges as a clinically proven alternative that offers high efficacy, localized effect, and diminished negative factors. Electrochemotherapy involves the treatment of solid tumors by combining a non-permeable cytotoxic drug, such as bleomycin, with a locally administered pulsed electric field (PEF). It is crucial to employ this method effectively by utilizing optimal PEF protocols and drugs at concentrations that do not possess inherent cytotoxic properties. This review emphasizes an examination of diverse clinical practices of ECT concerning head and neck cancer. It specifically delves into the treatment procedure, the choice of anti-cancer drugs, pre-treatment planning, PEF protocols, and electroporation electrodes as well as the efficacy of tumor response to the treatment and encountered obstacles. We have also highlighted the significance of assessing the spatial electric field distribution in both tumor and adjacent tissues prior to treatment as it plays a pivotal role in determining treatment success. Finally, we compare the ECT methodology to conventional treatments to highlight the potential for improvement and to facilitate popularization of the technique in the area of head and neck cancers where it is not widespread yet while it is not the case with other cancer types.

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Calcium electroporation causes ATP depletion in cells and is effective both in microsecond and nanosecond pulse range as a modality of electrochemotherapy

Cited by 3 publications

References 42 publications

Determination of the Impact of High-Intensity Pulsed Electromagnetic Fields on the Release of Damage-Associated Molecular Pattern Molecules

Determination of the Impact of High-Intensity Pulsed Electromagnetic Fields on the Release of Damage-Associated Molecular Pattern Molecules

Mitochondrial depolarization and ATP loss during high frequency nanosecond and microsecond electroporation

Electrochemotherapy for head and neck cancers: possibilities and limitations

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