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Strahlentherapie und Onkologie

Published in:

01-09-2014 | Original article

DNA fragmentation and caspase-independent programmed cell death by modulated electrohyperthermia

Authors: N. Meggyeshazi, G. Andocs, L. Balogh, P. Balla, G. Kiszner, I. Teleki, A. Jeney, T. Krenacs, PhD

Published in: Strahlentherapie und Onkologie | Issue 9/2014

Abstract

Background and purpose

The electric field and the concomitant heat (electrohyperthermia) can synergistically induce cell death in tumor tissue, due to elevated glycolysis, ion concentration, and permittivity in malignant compared with nonmalignant tissues. Here we studied the mechanism and time course of tumor destruction caused by electrohyperthermia.

Material and methods

Bilateral implants of HT29 colorectal cancer in the femoral regions of Balb/c (nu/nu) mice were treated with a single 30-min shot of modulated, 13.56-MHz, radiofrequency-generated electrohyperthermia (mEHT). Tumors at 0, 1, 4, 8, 14, 24, 48, and 72 h posttreatment were studied for morphology, DNA fragmentation, and cell death response-related protein expression using tissue microarrays, immunohistochemistry, Western immunoblots, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays.

Results

Modulated EHT treatment induced significant tumor destruction in HT29 xenografts with a peak of a sevenfold increase compared with the untreated controls. The significant treatment-related elevation of DNA fragmentation—detected with TUNEL assay—and apoptotic bodies between 24 and 72 h posttreatment was proof of a programmed cell death response. This was associated with significant mitochondrial accumulation of bax and mitochondrial-to-cytoplasmic release of cytochrome c proteins between 8 and 14 h. Cleaved caspase-3 levels were low and mainly localized to inflammatory cells. The substantial cytoplasmic-to-nuclear translocation of apoptosis-inducing factor (AIF) and its 57-kDa activated fragment detected between 14 and 24 h after treatment indicated AIF as an effector for DNA fragmentation.

Conclusion

Modulated EHT treatment can induce programmed cell death-related tumor destruction in HT29 colorectal adenocarcinoma xenografts, which dominantly follows a caspase-independent subroutine.

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Title: DNA fragmentation and caspase-independent programmed cell death by modulated electrohyperthermia
Authors: N. Meggyeshazi
G. Andocs
L. Balogh
P. Balla
G. Kiszner
I. Teleki
A. Jeney
T. Krenacs, PhD
Publication date: 01-09-2014
Publisher: Springer Berlin Heidelberg
Published in: Strahlentherapie und Onkologie / Issue 9/2014
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-014-0617-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

DNA fragmentation and caspase-independent programmed cell death by modulated electrohyperthermia

Abstract

Background and purpose

Material and methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background and purpose

Material and methods

Results

Conclusion

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