AS601245 - CAS 345987-15-7
Catalog number: 345987-15-7
Category: Inhibitor
Not Intended for Therapeutic Use. For research use only.
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AS601245; AS-601245; AS 601245.
1.AS601245, an Anti-Inflammatory JNK Inhibitor, and Clofibrate Have a Synergistic Effect in Inducing Cell Responses and in Affecting the Gene Expression Profile in CaCo-2 Colon Cancer Cells.
Cerbone A1, Toaldo C, Pizzimenti S, Pettazzoni P, Dianzani C, Minelli R, Ciamporcero E, Roma G, Dianzani MU, Canaparo R, Ferretti C, Barrera G. PPAR Res. 2012;2012:269751. doi: 10.1155/2012/269751. Epub 2012 Feb 29.
PPARαs are nuclear receptors highly expressed in colon cells. They can be activated by the fibrates (clofibrate, ciprofibrate etc.) used to treat hyperlipidemia. Since PPARα transcriptional activity can be negatively regulated by JNK, the inhibition of JNK activity could increase the effectiveness of PPARα ligands. We analysed the effects of AS601245 (a JNK inhibitor) and clofibrate alone or in association, on proliferation, apoptosis, differentiation and the gene expression profile of CaCo-2 human colon cancer cells. Proliferation was inhibited in a dose-dependent way by clofibrate and AS601245. Combined treatment synergistically reduced cell proliferation, cyclin D1 and PCNA expression and induced apoptosis and differentiation. Reduction of cell proliferation, accompanied by the modulation of p21 expression was observed in HepG2 cells, also. Gene expression analysis revealed that some genes were highly modulated by the combined treatment and 28 genes containing PPRE were up-regulated, while clofibrate alone was ineffective.
2.Rosiglitazone and AS601245 decrease cell adhesion and migration through modulation of specific gene expression in human colon cancer cells.
Cerbone A1, Toaldo C, Minelli R, Ciamporcero E, Pizzimenti S, Pettazzoni P, Roma G, Dianzani MU, Ullio C, Ferretti C, Dianzani C, Barrera G. PLoS One. 2012;7(6):e40149. doi: 10.1371/journal.pone.0040149. Epub 2012 Jun 28.
PPARs are nuclear receptors activated by ligands. Activation of PPARγ leads to a reduction of adhesion and motility in some cancer models. PPARγ transcriptional activity can be negatively regulated by JNK-mediated phosphorylation. We postulated that the use of agents able to inhibit JNK activity could increase the effectiveness of PPARγ ligands. We analysed the effects of rosiglitazone (PPARγ ligand) and AS601245 (a selective JNK inhibitor) alone or in association on adhesion and migration of CaCo-2, HT29, and SW480 human colon cancer cells and investigated, through microarray analysis, the genes involved in these processes. Cell adhesion and migration was strongly inhibited by rosiglitazone and AS601245. Combined treatment with the two compounds resulted in a greater reduction of the adhesion and migration capacity. Affymetrix analysis in CaCo-2 cells revealed that some genes which were highly modulated by the combined treatment could be involved in these biological responses.
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