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Apoptosis initiation and angiogenesis inhibition: melanoma targets for nanosecond pulsed electric fields

  1. Xinhua Chen1,
  2. Juergen F. Kolb1,
  3. R. James Swanson1,2,
  4. Karl H. Schoenbach1,
  5. Stephen J. Beebe1,3

Article first published online: 2 APR 2010

DOI: 10.1111/j.1755-148X.2010.00704.x

Issue

Pigment Cell & Melanoma Research

Pigment Cell & Melanoma Research

Volume 23, Issue 4, pages 554–563, August 2010

Additional Information

How to Cite

Chen, X., Kolb, J. F., Swanson, R. J., Schoenbach, K. H. and Beebe, S. J. (2010), Apoptosis initiation and angiogenesis inhibition: melanoma targets for nanosecond pulsed electric fields. Pigment Cell & Melanoma Research, 23: 554–563. doi: 10.1111/j.1755-148X.2010.00704.x

Author Information

  1. 1

     Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA

  2. 2

     Department of Biology, Old Dominion University, Norfolk, VA, USA

  3. 3

     Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA, USA

*Stephen J. Beebe, e-mail: sbeebe@odu.edu

Publication History

  1. Issue published online: 16 JUL 2010
  2. Article first published online: 2 APR 2010
  3. PUBLICATION DATA Received 3 February 2010, revised and accepted for publication 30 March 2010, published online 2 April 2010

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Keywords:

  • electric fields;
  • non-thermal effects;
  • apoptosis;
  • angiogenesis;
  • caspases;
  • DNA damage;
  • DNA double strand breaks

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.

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