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Differential cellular effects of electroporation and electrochemotherapy in monolayers of human microvascular endothelial cells

In vivo electroporation of tumours shows disruption of blood flow and creates a vascular effect with an initial rapid and transient vasoconstriction phase and a much longer lasting phase with changed microvascular endothelium. These changes are not well understood but are presumed to involve the cyt...

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Published in:PloS one 2012-12, Vol.7 (12), p.e52713-e52713
Main Authors: Meulenberg, Cécil J W, Todorovic, Vesna, Cemazar, Maja
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description In vivo electroporation of tumours shows disruption of blood flow and creates a vascular effect with an initial rapid and transient vasoconstriction phase and a much longer lasting phase with changed microvascular endothelium. These changes are not well understood but are presumed to involve the cytoskeleton. The paper presents for the first time differential in vitro effects describing cytoskeleton changes and monolayer integrity changes by both electroporation and electrochemotherapy of monolayers of human microvascular endothelial cells (HMEC-1). After the application of electric field pulses, the morphology of cells, and both the F-actin and Beta-tubulin cytoskeleton proteins were affected. During both electroporation and electrochemotherapy, the initial phase of cellular damage was noticed at 10 min as swollen cells and honeycomb-like actin bundles. The electroporation-induced cellular effects, observed from electric pulses >150 V, were voltage-dependent and within 24 hrs partly recoverable. The electrochemotherapy-induced cellular effects developed at 2 hrs in spindle-like cells, and more densely packed F-actin and Beta-tubulin were observed, which were dependent on the amount of bleomycin and the voltages applied (>50 V). In addition, for electrochemotherapy with electric pulses >150 V cellular changes were not recoverable within 24 hrs. The effects on monolayer integrity were reflected in the enhanced monolayer permeability, with the electrochemotherapy showing an earlier onset and synergy. We conclude that electrochemotherapy as compared to electroporation leads within 24 hrs to a quicker and more pronounced monolayer integrity damage and endothelial cell death, which together provide further insight into the cellular changes of the vascular disruption of electrochemotherapy.
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subjects Actin
Actin Cytoskeleton - metabolism
Actins - metabolism
Analysis
Antibiotics, Antineoplastic - metabolism
Biology
Bleomycin
Bleomycin - metabolism
Blood flow
Cancer
Capillary Permeability
Cell death
Cell Shape
Cells, Cultured
Cytoskeleton
Electric fields
Electric pulses
Electrochemotherapy
Electroporation
Endothelial cells
Endothelial Cells - drug effects
Endothelial Cells - physiology
Endothelium
Fibroblasts
Health sciences
Honeycomb construction
Humans
Integrity
Medicine
Membrane permeability
Microvasculature
Microvessels - pathology
Monolayers
Monomolecular films
Muscle proteins
Neoplasms - blood supply
Neoplasms - drug therapy
Oncology
Permeability
Phase transitions
Polymerization
Proteins
Tubulin
Tubulin - metabolism
Tumors
Vasoconstriction
title Differential cellular effects of electroporation and electrochemotherapy in monolayers of human microvascular endothelial cells
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