Emily H. Hall1, 2, 3,
Karl H. Schoenbach2 and Stephen J. Beebe1, 2 
(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 |
(2) |
Center for Bioelectrics, Old
Dominion University, Eastern Virginia Medical School, Norfolk, VA, USA |
(3) |
Present address: Department
of Microbiology, University of Virginia, Charlottesville, VA, USA |
Published online: 23 May 2007
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.
Keywords Non-ionizing
radiation - Apoptosis - Caspases - Cytochrome c - Bcl-2 family - p53
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.