Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells

D’Alise, Anna Morena; Amabile, Giovanni; Iovino, Mariangela; Giorgio, Francesco Paolo Di; Bartiromo, Marta; Sessa, Fabio; Villa, Fabrizio; Musacchio, Andrea; Cortese, Riccardo

doi:10.1158/1535-7163.mct-07-2051

Cited by 116 publications

(115 citation statements)

References 25 publications

(35 reference statements)

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“…35,[41][42][43][44][45] These findings indicate that reversine exerts relatively broad anticancer effects. Here, we show that low-dose reversine, 0.5 μM, a concentration at which reversine selectively inhibits MPS1, fails to preferentially kill TP53 -/-HCT 116 colon carcinoma cells.…”

Section: Discussionmentioning

confidence: 94%

Preferential killing of p53-deficient cancer cells by reversine

et al. 2012

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Section: Discussionmentioning

confidence: 94%

Preferential killing of p53-deficient cancer cells by reversine

et al. 2012

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“…D'Alise et al [29] showed that reversine acts as an inhibitor of Aurora kinases A and B, which have been implicated in mitosis, leading to defect in cytokinesis and induction of polyploidization. They also showed that reversine inhibits phosphorylation of histone H3, a direct downstream target of Aurora kinases.…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Reversine on In Vitro Development of Miniature Pig Somatic Cell Nuclear Transfer Embryos

Miyoshi

Mori

Mizobe

et al. 2010

Journal of Reproduction and Development

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Abstract. Reversine, a 2-(4-morpholinoanilino)-6-cyclohexylaminopurine analog, can induce dedifferentiation of myogenic lineage-committed cells into multipotent mesenchymal progenitor cells, from which osteoblasts and adipocytes redifferentiate under lineage-specific inducing conditions. Although the molecular mechanism of how reversine causes dedifferentiation of a differentiated cell has not been fully elucidated, we speculated that it would be involved in reprogramming. In the present study, we examined whether reversine can enhance the development of somatic cell nuclear transfer (SCNT) embryos by improving the reprogramming state of the somatic cell nuclei. As donor cells, we used miniature pig fetal fibroblasts transfected with a plasmid construct containing a mouse Oct-3/4 promoter and enhanced green fluorescent protein (EGFP) cDNA. When the nuclei of these transfected cells are reprogrammed to an undifferentiated state in the SCNT embryos, EGFP expression is expected to commence under the control of the Oct-3/4 promoter. After SCNT, the resulting embryos were treated with 5 μM reversine for different durations (0, 6, 12, 18 and 24 h) or at different concentrations (0, 1, 5 and 10 μM) of reversine for 12 h and then cultured in vitro. When embryos were treated with 5 μM reversine for 12 h, the blastocyst formation rate was significantly (P<0.01) higher than that of embryos without reversine treatment. However, the strength and pattern of EGFP expression in the embryos were not affected by the same treatment. A normal-looking fetus was obtained 21 days after transfer of embryos treated with 5 μM reversine for 12 h into recipients. The present findings indicate that treatment with reversine is beneficial for enhancement of the in vitro development of miniature pig SCNT embryos, although the underlying mechanism is still unclear. Key words: In vitro development, Miniature pig, Reprogramming, Reversine, Somatic cell nuclear transfer (J. Reprod. Dev. 56: [291][292][293][294][295][296] 2010) ecently, Chen et al. [1] reported that a 2-(4-morpholinoanilino)-6-cyclohexylaminopurine analog could induce dedifferentiation of myogenic lineage-committed C2C12 cells to become multipotent mesenchymal progenitor cells in the concentration range of 1-10 μM. These progenitor cells could redifferentiate into osteoblasts or adipocytes under appropriate differentiation inducing conditions. The compound was named "reversine" because of its ability to reverse terminally differentiated cells to progenitor cells [1]. More recently, it was reported that human fibroblasts treated with reversine exhibited redifferentiation into skeletal muscle cells in vitro and in vivo [2]. Thus, reversine has the ability to reprogram somatic cells to a state of diverse plasticity that can be manipulated to differentiation into different cell types.Low cloning efficiency, which is often associated with low developmental rate of somatic cell nuclear transfer (SCNT) embryos, remains the major obstacle to use this technology in various fields of ani...

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“…This chemical compound was reported to induce reversal of mouse myoblast cell line, C2C12, to become multipotent progenitor cells, which can re-differentiate into osteoblasts and adipocytes (Chen et al, 2004). The de-differentiation activity of reversine however is not conserved across all cell lineages, since in certain cell types, it acts as a potent differentiation-inducing molecule (D'Alise et al, 2008).…”

Section: Obtaining Hsc From Escmentioning

confidence: 99%