Reversine, a synthetic purine isolated from a combinatorial library, has been shown to induce the de-differentiation of adult cells, including fibroblasts, to stem-cell-like progenitors, as treated cells could be induced to differentiate into several cell types, thus creating a new stem cell source for tissue regeneration. The observation that reversine treatment, while inducing cell reprogramming, also caused growth arrest, suggested its possible application as an anticancer agent. Herein we reported reversine lethal effects on several tumor cells from different tissues and we clarified the mechanism of cell death induced by the molecule. Moreover, this molecule seems to be selective for cancer cells because of the lack of the induction of cell death in normal fibroblast with the same condition of treatment. Comparison of reversine effects on the cell cycle of normal and cancer cells also elucidated the mechanism of its dual activity as de-differentiating or anti-cancer drug, depending on the cell type and the status of the cell cycle checkpoints.
INDUZIONE SELETTIVA DI MORTE CELLULARE PER CATASTROFE MITOTICA IN CELLULE TUMORALI: EFFETTI DELLA PURINA SINTETICA REVERSINA / M. Piccoli ; relatore: Paola Viani ; correlatore: Luigi Anastasia ; coordinatore: Enrico Ginelli. Universita' degli Studi di Milano, 2010 Dec 20. 23. ciclo, Anno Accademico 2010. [10.13130/piccoli-marco_phd2010-12-20].
INDUZIONE SELETTIVA DI MORTE CELLULARE PER CATASTROFE MITOTICA IN CELLULE TUMORALI: EFFETTI DELLA PURINA SINTETICA REVERSINA
M. Piccoli
2010
Abstract
Reversine, a synthetic purine isolated from a combinatorial library, has been shown to induce the de-differentiation of adult cells, including fibroblasts, to stem-cell-like progenitors, as treated cells could be induced to differentiate into several cell types, thus creating a new stem cell source for tissue regeneration. The observation that reversine treatment, while inducing cell reprogramming, also caused growth arrest, suggested its possible application as an anticancer agent. Herein we reported reversine lethal effects on several tumor cells from different tissues and we clarified the mechanism of cell death induced by the molecule. Moreover, this molecule seems to be selective for cancer cells because of the lack of the induction of cell death in normal fibroblast with the same condition of treatment. Comparison of reversine effects on the cell cycle of normal and cancer cells also elucidated the mechanism of its dual activity as de-differentiating or anti-cancer drug, depending on the cell type and the status of the cell cycle checkpoints.File | Dimensione | Formato | |
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