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Apoptosis initiation and angiogenesis inhibition: melanoma targets for nanosecond pulsed electric fields
Author(s) -
Chen Xinhua,
Kolb Juergen F.,
Swanson R. James,
Schoenbach Karl H.,
Beebe Stephen J.
Publication year - 2010
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2010.00704.x
Subject(s) - angiogenesis , apoptosis , dna fragmentation , in vivo , cancer research , terminal deoxynucleotidyl transferase , chemistry , caspase , microbiology and biotechnology , cd31 , programmed cell death , biology , tunel assay , biochemistry
Summary 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.