Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells

Overview

Journal Sci Rep

Specialty Science

Date 2015 Dec 15

PMID 26658786

Citations 147

Authors

Moshe Giladi

Rosa S Schneiderman

Tali Voloshin

Yaara Porat

Mijal Munster

Roni Blat

Shay Sherbo

Zeev Bomzon

Noa Urman

Aviran Itzhaki

Shay Cahal

Anna Shteingauz

Aafia Chaudhry

Eilon D Kirson

Uri Weinberg

Yoram Palti

Affiliations

Soon will be listed here.

Abstract

Tumor Treating Fields (TTFields) are low intensity, intermediate frequency, alternating electric fields. TTFields are a unique anti-mitotic treatment modality delivered in a continuous, noninvasive manner to the region of a tumor. It was previously postulated that by exerting directional forces on highly polar intracellular elements during mitosis, TTFields could disrupt the normal assembly of spindle microtubules. However there is limited evidence directly linking TTFields to an effect on microtubules. Here we report that TTFields decrease the ratio between polymerized and total tubulin, and prevent proper mitotic spindle assembly. The aberrant mitotic events induced by TTFields lead to abnormal chromosome segregation, cellular multinucleation, and caspase dependent apoptosis of daughter cells. The effect of TTFields on cell viability and clonogenic survival substantially depends upon the cell division rate. We show that by extending the duration of exposure to TTFields, slowly dividing cells can be affected to a similar extent as rapidly dividing cells.

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