Exclusive destruction of mitotic spindles in human cancer cells

// Leonid Visochek 1 , Asher Castiel 2 , Leonid Mittelman 3 , Michael Elkin 4 , Dikla Atias 2 , Talia Golan 2 , Shai Izraeli 2, 5 , Tamar Peretz 4 , Malka Cohen-Armon 1, 6 1 The Neufeld Cardiac Research Institute, Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel 2 Cancer Research Center, Sheba Medical Center, Ramat Gan 53621, Israel 3 The Imaging Unit, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel 4 Sharett Oncology Institute, Hadassah Medical Center, Ein-Kerem, Jerusalem 91120, Israel 5 The Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel 6 Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv 69978, Israel Correspondence to: Malka Cohen-Armon, email: marmon@post.tau.ac.il 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.