The Evidence of the Bystander Effect after Bleomycin Electrotransfer and Irreversible Electroporation

Ruzgys, Paulius; Barauskaitė, Neringa; Novickij, Vitalij; Novickij, Jurij; Šatkauskas, Saulius

doi:10.3390/molecules26196001

Cited by 7 publications

(6 citation statements)

References 57 publications

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“…In a recent study, we demonstrated the presence of the bystander effect after bleomycin electrotransfer in CHO cells [ 37 ]. In the present study, we aimed to build on the previous results and analyze the bystander effect on 4T1 cells after bleomycin electrotransfer and after calcium electroporation.…”

Section: Resultsmentioning

confidence: 99%

“…In our recent study, we demonstrated the negative bystander effect on CHO cells after bleomycin electrotransfer and hypothesized that the negative bystander effect could be triggered by a similar mechanism to the bystander effect induced by ionizing irradiation [ 37 , 43 , 44 ]. In this study, we extended analysis of the bystander effect and for the first time showed the presence of bystander effect on 4T1 cells after calcium electroporation ( Figure 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…Synthesis and release of damage-associated molecular patterns (DAMPs) [ 30 , 35 , 36 ] following electroporation is the most common explanation of how electroporation-based cancer treatments can induce immune responses. In our recent study, we demonstrated that bleomycin electrotransfer can induce a negative bystander effect on cells that were not treated directly [ 37 ]. Interestingly, we showed that irreversible electroporation can trigger a positive bystander effect in vitro, presumably because of cell viability promoting factors released in the medium from irreversibly electroporated cells.…”

Section: Introductionmentioning

confidence: 99%

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Induction of Bystander and Abscopal Effects after Electroporation-Based Treatments

Ruzgys

Navickaitė

Palepšienė

et al. 2022

Cancers

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Electroporation-based antitumor therapies, including bleomycin electrotransfer, calcium electroporation, and irreversible electroporation, are very effective on directly treated tumors, but have no or low effect on distal nodules. In this study, we aimed to investigate the abscopal effect following calcium electroporation and bleomycin electrotransfer and to find out the effect of the increase of IL-2 serum concentration by muscle transfection. The bystander effect was analyzed in in vitro studies on 4T1tumor cells, while abscopal effect was investigated in an in vivo setting using Balb/c mice bearing 4T1 tumors. ELISA was used to monitor IL-2 serum concentration. We showed that, similarly to cell treatment with bleomycin electrotransfer, the bystander effect occurs also following calcium electroporation and that these effects can be combined. Combination of these treatments also resulted in the enhancement of the abscopal effect in vivo. Since these treatments resulted in an increase of IL-2 serum concentration only in mice bearing one but not two tumors, we increased IL-2 serum concentration by muscle transfection. Although this did not enhance the abscopal effect of combined tumor treatment using calcium electroporation and bleomycin electrotransfer, boosting of IL-2 serum concentration had a significant inhibitory effect on directly treated tumors.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Induction of Bystander and Abscopal Effects after Electroporation-Based Treatments

Ruzgys

Navickaitė

Palepšienė

et al. 2022

Cancers

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“…Interestingly, cells which are not in between electrodes can also be affected by PEFs application. This phenomenon is called a “Bystander effect” 33 . To our knowledge, no thorough studies were carried out which characterized molecular changes in cells in close proximity to sub-electroporation threshold electric fields range.…”

Section: Discussionmentioning

confidence: 99%

Nanosecond pulsed electric field suppresses growth and reduces multi-drug resistance effect in pancreatic cancer

Szlasa

Michel

Sauer

et al. 2023

Sci Rep

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Nanosecond pulsed electric fields (nsPEF) have been shown to exert anticancer effects; however, little is known about the mechanisms triggered in cancer cells by nanosecond-length pulses, especially when low, sub-permeabilization voltage is used. In this study, three human pancreatic cancer cell lines were treated with nsPEF and molecular changes at the cellular level were analyzed. Further, we assessed the efficacy of paclitaxel chemotherapy following nsPEF treatment and correlated that with the changes in the expression of multi-drug resistance (MDR) proteins. Finally, we examined the influence of nsPEF on the adhesive properties of cancer cells as well as the formation and growth of pancreatic cancer spheroids. Cell line response differed with the application of a 200 ns, 100 pulses, 8 kV/cm, 10 kHz PEF treatment. PEF treatment led to (1) the release of microvesicles (MV) in EPP85-181RDB cells, (2) electropermeabilization in EPP85-181RNOV cells and (3) cell shrinkage in EPP85-181P cells. The release of MV’s in EPP85-181RDB cells reduced the membrane content of P-gp and LRP, leading to a transient increase in vulnerability of the cells towards paclitaxel. In all cell lines we observed an initial reduction in size of the cancer spheroids after the nsPEF treatment. Cell line EPP85-181RNOV exhibited a permanent reduction in the spheroid size after nsPEF. We propose a mechanism in which the surface tension of the membrane, regulated by the organization of actin fibers, modulates the response of cancer cells towards nsPEF. When a membrane’s surface tension remains low, we observed some cells form protrusions and release MVs containing MDR proteins. In contrast, when cell surface tension remains high, the cell membrane is being electroporated. The latter effect may be responsible for the reduced tumor growth following nsPEF treatment.

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“…Interestingly, cells which are not in between electrodes can also be affected by PEFs application. This phenomenon is called a "Bystander effect" [34]. To our knowledge, no thorough studies were carried out which characterized molecular changes in cells in close proximity to sub-electroporation threshold electric elds range.…”

Section: Discussionmentioning

confidence: 99%

Nanosecond Pulsed Electric Field Suppresses Growth and Reduces Multi-drug Resistance Effect in Pancreatic Cancer

Szlasa

Michel

Sauer

et al. 2023

Preprint

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Nanosecond pulsed electric fields (nsPEF) have been shown to exert anticancer effects; however, little is known about the mechanisms triggered in cancer cells by nanosecond-length pulses, especially when low, sub-permeabilization voltage is used. In this study, three human pancreatic cancer cell lines were treated with nsPEF and molecular changes at the cellular level were analyzed. Further, we assessed the efficacy of paclitaxel chemotherapy following nsPEF treatment and correlated that with the changes in the expression of multi-drug resistance (MDR) proteins. Finally, we examined the influence of nsPEF on the adhesive properties of cancer cells as well as the formation and growth of pancreatic cancer spheroids. Cell line response differed with the application of a 200 ns, 100 pulses, 8 kV/cm, 10 kHz PEF treatment. PEF treatment led to 1) the release of microvesicles (MV) in EPP85-181RDB cells, 2) electropermeabilization in EPP85-181RNOV cells and 3) cell shrinkage in EPP85-181P cells. The release of MV’s in EPP85-181RDB cells reduced the membrane content of P-gp and LRP, leading to a transient increase in vulnerability of the cells towards paclitaxel. In all cell lines we observed an initial reduction in size of the cancer spheroids after the nsPEF treatment. Cell line EPP85-181RNOV exhibited a permanent reduction in the spheroid size after nsPEF. We propose a mechanism in which the surface tension of the membrane, regulated by the organization of actin fibers, modulates the response of cancer cells towards nsPEF. When a membrane’s surface tension remains low, we observed some cells form protrusions and release MVs containing MDR proteins. In contrast, when cell surface tension remains high, the cell membrane is being electroporated. The latter effect may be responsible for the reduced tumor growth following nsPEF treatment.

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The Evidence of the Bystander Effect after Bleomycin Electrotransfer and Irreversible Electroporation

Cited by 7 publications

References 57 publications

Induction of Bystander and Abscopal Effects after Electroporation-Based Treatments

Induction of Bystander and Abscopal Effects after Electroporation-Based Treatments

Nanosecond pulsed electric field suppresses growth and reduces multi-drug resistance effect in pancreatic cancer

Nanosecond Pulsed Electric Field Suppresses Growth and Reduces Multi-drug Resistance Effect in Pancreatic Cancer

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