Exclusive destruction of mitotic spindles in human cancer cells

Leonid Visochek; Asher Castiel; Leonid Mittelman; Michael Elkin; Dikla Atias; Talia Golan; Shai Izraeli; Tamar Peretz; Malka Cohen-Armon

doi:10.18632/oncotarget.15343

Exclusive destruction of mitotic spindles in human cancer cells

Leonid Visochek, Asher Castiel, Leonid Mittelman, Michael Elkin, Dikla Atias, Talia Golan, Shai Izraeli, Tamar Peretz, Malka Cohen-Armon^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

We identified target proteins modified by phenanthrenes that cause exclusive eradication of human cancer cells. The cytotoxic activity of the phenanthrenes in a variety of human cancer cells is attributed by these findings to post translational modifications of NuMA and kinesins HSET/kifC1 and kif18A. Their activity prevented the binding of NuMA to α-tubulin and kinesins in human cancer cells, and caused aberrant spindles. The most efficient cytotoxic activity of the phenanthridine PJ34, caused significantly smaller aberrant spindles with disrupted spindle poles and scattered extra-centrosomes and chromosomes. Concomitantly, PJ34 induced tumor growth arrest of human malignant tumors developed in athymic nude mice, indicating the relevance of its activity for cancer therapy.

Original language	English
Pages (from-to)	20813-20824
Number of pages	12
Journal	Oncotarget
Volume	8
Issue number	13
DOIs	https://doi.org/10.18632/oncotarget.15343
State	Published - 2017

Keywords

Human cancer cells
Kinesins
Mitotic spindles
NuMA
Phenanthrenes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.15343

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title = "Exclusive destruction of mitotic spindles in human cancer cells",

abstract = "We identified target proteins modified by phenanthrenes that cause exclusive eradication of human cancer cells. The cytotoxic activity of the phenanthrenes in a variety of human cancer cells is attributed by these findings to post translational modifications of NuMA and kinesins HSET/kifC1 and kif18A. Their activity prevented the binding of NuMA to α-tubulin and kinesins in human cancer cells, and caused aberrant spindles. The most efficient cytotoxic activity of the phenanthridine PJ34, caused significantly smaller aberrant spindles with disrupted spindle poles and scattered extra-centrosomes and chromosomes. Concomitantly, PJ34 induced tumor growth arrest of human malignant tumors developed in athymic nude mice, indicating the relevance of its activity for cancer therapy.",

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AU - Visochek, Leonid

AU - Castiel, Asher

AU - Mittelman, Leonid

AU - Elkin, Michael

AU - Atias, Dikla

AU - Golan, Talia

AU - Izraeli, Shai

AU - Peretz, Tamar

AU - Cohen-Armon, Malka

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AB - We identified target proteins modified by phenanthrenes that cause exclusive eradication of human cancer cells. The cytotoxic activity of the phenanthrenes in a variety of human cancer cells is attributed by these findings to post translational modifications of NuMA and kinesins HSET/kifC1 and kif18A. Their activity prevented the binding of NuMA to α-tubulin and kinesins in human cancer cells, and caused aberrant spindles. The most efficient cytotoxic activity of the phenanthridine PJ34, caused significantly smaller aberrant spindles with disrupted spindle poles and scattered extra-centrosomes and chromosomes. Concomitantly, PJ34 induced tumor growth arrest of human malignant tumors developed in athymic nude mice, indicating the relevance of its activity for cancer therapy.

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KW - Mitotic spindles

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KW - Phenanthrenes

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Exclusive destruction of mitotic spindles in human cancer cells

Abstract

Keywords

UN SDGs

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