Atorvastatin Modulates the Efficacy of Electroporation and Calcium Electrochemotherapy

Szlasa, Wojciech; Szewczyk, Anna; Novickij, Vitalij; Tarek, Mounir; Łapińska, Zofia; Saczko, Jolanta; Kulbacka, Julita; Rembiałkowska, Nina

doi:10.3390/ijms222011245

Cited by 10 publications

(9 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, in EPP85-181RDB cells, peripherally aligned F-actin bers were disrupted following the nsPEF treatment, which reduced the surface tension of the membrane. The surface tension is also affected by the lipid composition of the cancer cell membrane [39]. Our molecular dynamics simulations showed that the reduced surface tension of the membrane leads to its invagination of the membrane and further the MVs release.…”

Section: Discussionmentioning

confidence: 80%

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

Szlasa

Michel

Sauer

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 80%

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

Szlasa

Michel

Sauer

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, in EPP85-181RDB cells, peripherally aligned F-actin fibers were disrupted following the nsPEF treatment, which reduced the surface tension of the membrane. The surface tension is also affected by the lipid composition of the cancer cell membrane 38 . Our molecular dynamics simulations showed that the reduced surface tension of the membrane leads to its invagination of the membrane and further the MVs release.…”

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…The first effect was widely described in the Jurkat cell line, in which the nanosecond pulses induced the permeabilization of the mitochondrial outer membrane and, therefore, the release of cytochrome c and reactive oxygen species to the cytoplasm ( 138 ). After the disruption of cell membrane integrity, the cell increases the biosynthesis of the components of its cytoskeleton ( 139 ). However, in short-term response, Kiełbik et al.…”

Section: Physical Methods and Their Mechanismsmentioning

confidence: 99%

Chemotherapy and Physical Therapeutics Modulate Antigens on Cancer Cells

et al. 2022

View full text Add to dashboard Cite

Cancer cells possess specific properties, such as multidrug resistance or unlimited proliferation potential, due to the presence of specific proteins on their cell membranes. The release of proliferation-related proteins from the membrane can evoke a loss of adaptive ability in cancer cells and thus enhance the effects of anticancer therapy. The upregulation of cancer-specific membrane antigens results in a better outcome of immunotherapy. Moreover, cytotoxic T-cells may also become more effective when stimulated ex-vivo toward the anticancer response. Therefore, the modulation of membrane proteins may serve as an interesting attempt in anticancer therapy. The presence of membrane antigens relies on various physical factors such as temperature, exposure to radiation, or drugs. Therefore, changing the tumor microenvironment conditions may lead to cancer cells becoming sensitized to subsequent therapy. This paper focuses on the therapeutic approaches modulating membrane antigens and enzymes in anticancer therapy. It aims to analyze the possible methods for modulating the antigens, such as pharmacological treatment, electric field treatment, photodynamic reaction, treatment with magnetic field or X-ray radiation. Besides, an overview of the effects of chemotherapy and immunotherapy on the immunophenotype of cancer cells is presented. Finally, the authors review the clinical trials that involved the modulation of cell immunophenotype in anticancer therapy.

show abstract

Atorvastatin Modulates the Efficacy of Electroporation and Calcium Electrochemotherapy

Cited by 10 publications

References 65 publications

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

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

Chemotherapy and Physical Therapeutics Modulate Antigens on Cancer Cells

Contact Info

Product

Resources

About