title: Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells.
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.
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Giladi
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Rosa S
authors.initials: RS
authors.lastname: Schneiderman
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Voloshin
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Yaara
authors.initials: Y
authors.lastname: Porat
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Mijal
authors.initials: M
authors.lastname: Munster
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Roni
authors.initials: R
authors.lastname: Blat
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Sherbo
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Bomzon
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Urman
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Aviran
authors.initials: A
authors.lastname: Itzhaki
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Cahal
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Anna
authors.initials: A
authors.lastname: Shteingauz
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Aafia
authors.initials: A
authors.lastname: Chaudhry
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Eilon D
authors.initials: ED
authors.lastname: Kirson
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Weinberg
authors.affiliation: Novocure Ltd. Topaz Building, MATAM center Haifa 31905, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Palti
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D020090:Chromosome Segregation / Q000502:physiology*; D004560:Electricity; D006801:Humans; D061986:MCF-7 Cells; D008870:Microtubules / Q000378:metabolism / Q000473:pathology; D008938:Mitosis / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D008941:Spindle Apparatus / Q000473:pathology*; D014404:Tubulin / Q000378:metabolism
chemical_list: D014404:Tubulin