Application of Pulsed Electric Fields to Cancer Therapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Nuccitelli R
PROVIDER: S-EPMC8370244 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:In the last few years, pulsed electric fields have emerged as promising clinical tools for tumor treatments. This study highlights the distinct impact of a specific pulsed electric field protocol named PEF-5 (0.3 MV/m, 40 µs, 5 pulses) on astrocytes (NHA), medulloblastoma (D283) and gli-oblastoma (U87 NS) cancer stem-like cells. We pursued this goal performing ultrastructural analyses corroborated by molecular/omics approaches to understand the vulnerability or re-sistance mechanisms triggered by PEF-5 exposure in the different cell types. Electron microscopic analyses showed that, independently of exposed cells, the main targets of PEF-5 were the cell membrane and the cytoskeleton, presenting indiscriminate filopodia disappearance on the cell surface accompanied by a rapid cell swelling. Nevertheless, cells activated different responses stemming from intracellular organelles. NHA triggered a protective mechanism to recover from the damaged membranes and eliminated the detrimental ROS to maintain cell vital functions. Conversely, PEF-5 induced a different action on mitochondria of cancer stem-like cells, more prominent on D283 compared to U87 NS cells, in correlation with a higher basal level of CD133 protein in D283 cells. In this case, a complete mitochondrial dysfunction was demonstrated, inhibiting the recovery of D283 vital processes, while a mild perturbation was observed in mito-chondria of U87 NS cells, not sufficient to impair their cell functions. Altogether, these results suggest the possibility to use PEF-based technology as a novel strategy to target selectively mi-tochondria of CSCs, preserving healthy cells. Ultrastructural analysis, supported by transcriptomic characterization in microsecond pulsed electric field exposed normal brain and brain tumor cells
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Project description:In the last few years, pulsed electric fields have emerged as promising clinical tools for tumor treatments. This study highlights the distinct impact of a specific pulsed electric field protocol named PEF-5 (0.3 MV/m, 40 µs, 5 pulses) on astrocytes (NHA), medulloblastoma (D283) and gli-oblastoma (U87 NS) cancer stem-like cells. We pursued this goal performing ultrastructural analyses corroborated by molecular/omics approaches to understand the vulnerability or re-sistance mechanisms triggered by PEF-5 exposure in the different cell types. Electron microscopic analyses showed that, independently of exposed cells, the main targets of PEF-5 were the cell membrane and the cytoskeleton, presenting indiscriminate filopodia disappearance on the cell surface accompanied by a rapid cell swelling. Nevertheless, cells activated different responses stemming from intracellular organelles. NHA triggered a protective mechanism to recover from the damaged membranes and eliminated the detrimental ROS to maintain cell vital functions. Conversely, PEF-5 induced a different action on mitochondria of cancer stem-like cells, more prominent on D283 compared to U87 NS cells, in correlation with a higher basal level of CD133 protein in D283 cells. In this case, a complete mitochondrial dysfunction was demonstrated, inhibiting the recovery of D283 vital processes, while a mild perturbation was observed in mito-chondria of U87 NS cells, not sufficient to impair their cell functions. Altogether, these results suggest the possibility to use PEF-based technology as a novel strategy to target selectively mi-tochondria of CSCs, preserving healthy cells. Ultrastructural analysis, supported by transcriptomic characterization in microsecond pulsed electric field exposed normal brain and brain tumor cells.
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