Exclusive destruction of mitotic spindles in human cancer cells
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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
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
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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