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The synthetic purine reversine selectively induces cell death of cancer cells
Authors:Piccoli Marco  Palazzolo Giacomo  Conforti Erika  Lamorte Giuseppe  Papini Nadia  Creo Pasquale  Fania Chiara  Scaringi Raffaella  Bergante Sonia  Tringali Cristina  Roncoroni Leda  Mazzoleni Stefania  Doneda Luisa  Galli Rossella  Venerando Bruno  Tettamanti Guido  Gelfi Cecilia  Anastasia Luigi
Affiliation:Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Milan, Italy; Laboratory of Stem Cell for Tissue Engineering, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
Abstract:The synthetic purine reversine has been shown to possess a dual activity as it promotes the de‐differentiation of adult cells, including fibroblasts, into stem‐cell‐like progenitors, but it also induces cell growth arrest and ultimately cell death of cancer cells, suggesting its possible application as an anti‐cancer agent. Aim of this study was to investigate the mechanism underneath reversine selectivity in inducing cell death of cancer cells by a comparative analysis of its effects on several tumor cells and normal dermal fibroblasts. We found that reversine is lethal for all cancer cells studied as it induces cell endoreplication, a process that malignant cells cannot effectively oppose due to aberrations in cell cycle checkpoints. On the other hand, normal cells, like dermal fibroblasts, can control reversine activity by blocking the cell cycle, entering a reversible quiescent state. However, they can be induced to become sensitive to the molecule when key cell cycle proteins, e.g., p53, are silenced. J. Cell. Biochem. 113: 3207–3217, 2012. © 2012 Wiley Periodicals, Inc.
Keywords:REVERSINE  CELL REPROGRAMMING  SMALL MOLECULES AND STEM CELLS  NEW ANTI‐CANCER DRUGS
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