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• W4361255276 abstract "<div>Abstract<p>The purpose of this study was to investigate the antiangiogenic and <i>in vivo</i> properties of the recently identified phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor Inositol(1,3,4,5,6) pentakisphosphate [Ins(1,3,4,5,6)P₅]. Because activation of the PI3K/Akt pathway is a crucial step in some of the events leading to angiogenesis, the effect of Ins(1,3,4,5,6)P₅ on basic fibroblast growth factor (FGF-2)–induced Akt phosphorylation, cell survival, motility, and tubulogenesis <i>in vitro</i> was tested in human umbilical vein endothelial cells (HUVEC). The effect of Ins(1,3,4,5,6)P₅ on FGF-2-induced angiogenesis <i>in vivo</i> was evaluated using s.c. implanted Matrigel in mice. In addition, the effect of Ins(1,3,4,5,6)P₅ on growth of ovarian carcinoma SKOV-3 xenograft was tested. Here, we show that FGF-2 induces Akt phosphorylation in HUVEC resulting in antiapoptotic effect in serum-deprived cells and increase in cellular motility. Ins(1,3,4,5,6)P₅ blocks FGF-2-mediated Akt phosphorylation and inhibits both survival and migration in HUVEC. Moreover, Ins(1,3,4,5,6)P₅ inhibits the FGF-2-mediated capillary tube formation of HUVEC plated on Matrigel and the FGF-2-induced angiogenic reaction in BALB/c mice. Finally, Ins(1,3,4,5,6)P₅ blocks the s.c. growth of SKOV-3 xenografted in nude mice to the same extent than cisplatin and it completely inhibits Akt phosphorylation <i>in vivo</i>. These data definitively identify the Akt inhibitor Ins(1,3,4,5,6)P₅ as a specific antiangiogenic and antitumor factor. Inappropriate activation of the PI3K/Akt pathway has been linked to the development of several diseases, including cancer, making this pathway an attractive target for therapeutic strategies. In this respect, Ins(1,3,4,5,6)P₅, a water-soluble, natural compound with specific proapoptotic and antiangiogenic properties, might result in successful anticancer therapeutic strategies.</p></div>" @default.
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• W4361255276 date "2023-03-30" @default.
• W4361255276 modified "2023-09-30" @default.
• W4361255276 title "Data from Inhibition of the Phosphatidylinositol 3-Kinase/Akt Pathway by Inositol Pentakisphosphate Results in Antiangiogenic and Antitumor Effects" @default.
• W4361255276 doi "https://doi.org/10.1158/0008-5472.c.6493824.v1" @default.
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