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2015 ; 5
(ä): 18046
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English Wikipedia
Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper
Chromosome Segregation and Mitotic Catastrophe in Cancer Cells
#MMPMID26658786
Giladi M
; Schneiderman RS
; Voloshin T
; Porat Y
; Munster M
; Blat R
; Sherbo S
; Bomzon Z
; Urman N
; Itzhaki A
; Cahal S
; Shteingauz A
; Chaudhry A
; Kirson ED
; Weinberg U
; Palti Y
Sci Rep
2015[Dec]; 5
(ä): 18046
PMID26658786
show ga
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.