title: The synthetic purine reversine selectively induces cell death of cancer cells.
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.
authors.affiliation: Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Piccoli
authors.forename: Giacomo
authors.initials: G
authors.lastname: Palazzolo
authors.forename: Erika
authors.initials: E
authors.lastname: Conforti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lamorte
authors.forename: Nadia
authors.initials: N
authors.lastname: Papini
authors.forename: Pasquale
authors.initials: P
authors.lastname: Creo
authors.forename: Chiara
authors.initials: C
authors.lastname: Fania
authors.forename: Raffaella
authors.initials: R
authors.lastname: Scaringi
authors.forename: Sonia
authors.initials: S
authors.lastname: Bergante
authors.forename: Cristina
authors.initials: C
authors.lastname: Tringali
authors.forename: Leda
authors.initials: L
authors.lastname: Roncoroni
authors.forename: Stefania
authors.initials: S
authors.lastname: Mazzoleni
authors.forename: Luisa
authors.initials: L
authors.lastname: Doneda
authors.forename: Rossella
authors.initials: R
authors.lastname: Galli
authors.forename: Bruno
authors.initials: B
authors.lastname: Venerando
authors.forename: Guido
authors.initials: G
authors.lastname: Tettamanti
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gelfi
authors.forename: Luigi
authors.initials: L
authors.lastname: Anastasia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D052160:Benzothiazoles / Q000494:pharmacology; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D016923:Cell Death; D054337:Cell Dedifferentiation; D049109:Cell Proliferation; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival; D062951:Endoreduplication; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects; D005354:Fibrosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D009025:Morpholines; D011687:Purines; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D014050:Toluene; C121565:pifithrin; D020169:Caspases; C484369:2-(4-morpholinoanilino)-6-cyclohexylaminopurine