The synthetic purine reversine selectively induces cell death of cancer cells |
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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 |
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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. |
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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. |
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Keywords: | REVERSINE CELL REPROGRAMMING SMALL MOLECULES AND STEM CELLS NEW ANTI‐CANCER DRUGS |
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