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Nanosecond pulsed electric fields induce apoptosis in p53-wildtype and p53-null HCT116 colon carcinoma cells

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Abstract

Non-ionizing radiation produced by nanosecond pulsed electric fields (nsPEFs) is an alternative to ionizing radiation for cancer treatment. NsPEFs are high power, low energy (non-thermal) pulses that, unlike plasma membrane electroporation, modulate intracellular structures and functions. To determine functions for p53 in nsPEF-induced apoptosis, HCT116p53+/+ and HCT116p53−/− colon carcinoma cells were exposed to multiple pulses of 60 kV/cm with either 60 ns or 300 ns durations and analyzed for apoptotic markers. Several apoptosis markers were observed including cell shrinkage and increased percentages of cells positive for cytochrome c, active caspases, fragmented DNA, and Bax, but not Bcl-2. Unlike nsPEF-induced apoptosis in Jurkat cells (Beebe et al. 2003a) active caspases were observed before increases in cytochrome c, which occurred in the presence and absence of Bax. Cell shrinkage occurred only in cells with increased levels of Bax or cytochrome c. NsPEFs induced apoptosis equally in HCT116p53+/+ and HCT116p53−/− cells. These results demonstrate that non-ionizing radiation produced by nsPEFs can act as a non-ligand agonist with therapeutic potential to induce apoptosis utilizing mitochondrial-independent mechanisms in HCT116 cells that lead to caspase activation and cell death in the presence or absence of p-53 and Bax.

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Author notes

  1. Emily H. Hall

    Present address: Department of Microbiology, University of Virginia, Charlottesville, VA, USA

Authors and Affiliations

  1. Center for Pediatric Research, Children’s Hospital of the King’s Daughters and Department of Physiological Sciences, Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA, 23501-1980, USA

    Emily H. Hall & Stephen J. Beebe

  2. Center for Bioelectrics, Old Dominion University, Eastern Virginia Medical School, Norfolk, VA, USA

    Emily H. Hall, Karl H. Schoenbach & Stephen J. Beebe

Authors
  1. Emily H. Hall
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  2. Karl H. Schoenbach
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  3. Stephen J. Beebe
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Corresponding author

Correspondence to Stephen J. Beebe.

Additional information

This work was supported by the U.S. Air Force Office of Scientific Research/DOD MURI grant on Subcellular Responses to Narrow Band and Wide Band Radio Frequency Radiation, administered by Old Dominion University, and the American Cancer Society.

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Hall, E.H., Schoenbach, K.H. & Beebe, S.J. Nanosecond pulsed electric fields induce apoptosis in p53-wildtype and p53-null HCT116 colon carcinoma cells. Apoptosis 12, 1721–1731 (2007). https://doi.org/10.1007/s10495-007-0083-7

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  • DOI: https://doi.org/10.1007/s10495-007-0083-7

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