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.

The synthetic purine reversine selectively induces cell death of cancer cells / M. Piccoli, G. Palazzolo, E. Conforti, G. Lamorte, N. Papini, P. Creo, C. Fania, R. Scaringi, S. Bergante, C. Tringali, L. Roncoroni, S. Mazzoleni, L. Doneda, R. Galli, B. Venerando, G. Tettamanti, C. Gelfi, L. Anastasia. - In: JOURNAL OF CELLULAR BIOCHEMISTRY. - ISSN 0730-2312. - 113:10(2012 Oct), pp. 3207-3217.

The synthetic purine reversine selectively induces cell death of cancer cells

M. Piccoli;G. Palazzolo;N. Papini;C. Fania;R. Scaringi;S. Bergante;C. Tringali;L. Roncoroni;L. Doneda;B. Venerando;G. Tettamanti;C. Gelfi
Penultimo
;
L. Anastasia
Ultimo
2012

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.
reversine; cell reprogramming; small molecules and stem cells; new anti-caner drugs
Settore BIO/10 - Biochimica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/177982
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