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An extract of the plant Dioscorea nipponica Makino and inhibitor of both the serine/threonine protein kinase Akt (protein kinase B) and members of the phosphatidylinositol 3-kinase (PI3K) family of lipid kinases, with potential antineoplastic and anti-metastatic activities. Dioscorea nipponica Makino extracted with ethyl acetate (DNE3) binds to and inhibits PI3K and Akt. This inhibits PI3K/Akt-mediated signaling and prevents both growth and survival of PI3K/Akt-overexpressing tumor cells. In addition, DNE3 increases the expression of tissue inhibitor of metalloproteinase-2 (TIMP-2), inhibits the secretion of matrix metalloproteinases (MMPs), primarily MMP-2 and MMP-9, and inhibits the serine protease urokinase (urokinase-type plasminogen activator; u-PA). This inhibits tumor cell invasion, migration, motility, and adhesion. This agent also inhibits the activation of both cAMP response element-binding (CREB) and activating protein-1 (AP-1), and increases the expression of IkappaB (IkB), which inhibits the activation of nuclear factor-kappa B (NF-kB). These processes further contribute to this agent\'s anti-tumor potential in susceptible tumor cells. Check for \'https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C115103\' active clinical trials using this agent. (\'http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C115103\' NCI Thesaurus)
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