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

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This article has been corrected. Correction in: Oncotarget. 2020; 11:1290-1291.

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 and Malka Cohen-Armon _

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Oncotarget. 2017; 8:20813-20824. https://doi.org/10.18632/oncotarget.15343

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Abstract

Leonid Visochek1, Asher Castiel2, Leonid Mittelman3, Michael Elkin4, Dikla Atias2, Talia Golan2, Shai Izraeli2,5, Tamar Peretz4, Malka Cohen-Armon1,6

1The Neufeld Cardiac Research Institute, Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel

2Cancer Research Center, Sheba Medical Center, Ramat Gan 53621, Israel

3The Imaging Unit, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel

4Sharett Oncology Institute, Hadassah Medical Center, Ein-Kerem, Jerusalem 91120, Israel

5The Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel

6Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv 69978, Israel

Correspondence to:

Malka Cohen-Armon, email: [email protected]

Keywords: human cancer cells, mitotic spindles, NuMA, kinesins, phenanthrenes

Received: April 05, 2016 Accepted: January 31, 2017 Published: February 15, 2017

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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Research Papers:

Exclusive destruction of mitotic spindles in human cancer cells

Abstract