Apoptosis initiation and angiogenesis inhibition: melanoma targets for nanosecond pulsed electric fields |
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Authors: | Xinhua Chen Juergen F. Kolb R. James Swanson Karl H. Schoenbach Stephen J. Beebe |
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Affiliation: | 1. Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA;2. Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA Department of Biology, Old Dominion University, Norfolk, VA, USA;3. Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA, USA |
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Abstract: | Many effective anti-cancer strategies target apoptosis and angiogenesis mechanisms. Applications of non-ionizing, nanosecond pulsed electric fields (nsPEFs) induce apoptosis in vitro and eliminate cancer in vivo; however in vivo mechanisms require closer analysis. These studies investigate nsPEF-induced apoptosis and anti-angiogenesis examined by fluorescent microscopy, immunoblots, and morphology. Six hours after treatment with one hundred 300 ns pulses at 40 kV/cm, cells transiently expressed active caspases indicating that caspase-mediated mechanisms. Three hours after treatment transient peaks in Histone 2AX phosphorylation coincided with terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells and pyknotic nuclei, suggesting caspase-independent mechanisms on nuclei/DNA. Large DNA fragments, but not 180 bp fragmentation ladders, were observed, suggesting incomplete apoptosis. Nevertheless, tumor weight and volume decreased and tumors disappeared. One week after treatment, vessel numbers, vascular endothelial growth factor (VEGF), platelet derived endothelial cell growth factor (PD-ECGF), CD31, CD35 and CD105 were decreased, indicating anti-angiogenesis. The nsPEFs activate multiple melanoma therapeutic targets, which is consistent with successes of nsPEF applications for tumor treatment in vivo as a new cancer therapeutic modality. |
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Keywords: | electric fields non-thermal effects apoptosis angiogenesis caspases DNA damage DNA double strand breaks |
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