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Int J Environ Res Public Health. 2016 Nov 12;13(11). pii: E1128.

An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields.

Author information

1
Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada. jackt@ualberta.ca.
2
Department of Physics, University of Alberta, Edmonton, AB T6G 2E1, Canada. jackt@ualberta.ca.
3
The Institute of Biophysics and Biomedical Engineering, Faculdade de Ciências, Universidade de Lisboa, Lisboa 1749-016, Portugal. cwenger@fc.ul.pt.
4
Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada. defriesen@ualberta.ca.
5
Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada. jordane.preto@gmail.com.

Abstract

Long-standing research on electric and electromagnetic field interactions with biological cells and their subcellular structures has mainly focused on the low- and high-frequency regimes. Biological effects at intermediate frequencies between 100 and 300 kHz have been recently discovered and applied to cancer cells as a therapeutic modality called Tumor Treating Fields (TTFields). TTFields are clinically applied to disrupt cell division, primarily for the treatment of glioblastoma multiforme (GBM). In this review, we provide an assessment of possible physical interactions between 100 kHz range alternating electric fields and biological cells in general and their nano-scale subcellular structures in particular. This is intended to mechanistically elucidate the observed strong disruptive effects in cancer cells. Computational models of isolated cells subject to TTFields predict that for intermediate frequencies the intracellular electric field strength significantly increases and that peak dielectrophoretic forces develop in dividing cells. These findings are in agreement with in vitro observations of TTFields' disruptive effects on cellular function. We conclude that the most likely candidates to provide a quantitative explanation of these effects are ionic condensation waves around microtubules as well as dielectrophoretic effects on the dipole moments of microtubules. A less likely possibility is the involvement of actin filaments or ion channels.

KEYWORDS:

TTFields; biological cells; cancer cells; electric fields; ions; microtubules

PMID:
27845746
PMCID:
PMC5129338
DOI:
10.3390/ijerph13111128
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Novocure had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

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