and angiogenesis a naturally occurring inhibitor of phosphatidylinositol - 3 - kinase signaling ) , is Solenopsis invicta

Phosphatidylinositol-3-kinase (PI3K), and its downstream effector Akt, or protein kinase Bα (PKBα), play a major regulatory role in control of apoptosis, proliferation, and angiogenesis. PI3K and Akt are amplified or overexpressed in a number of malignancies, including sarcomas, ovarian cancer, multiple myeloma, and melanoma. This pathway regulates production of the potent angiogenic factor vascular endothelial growth factor (VEGF), and protects tumor cells against both chemotherapy and reactive oxygeninduced apoptosis through phosphorylation of substrates such as apoptotic peptidase activating factor-1 (APAF-1), forkhead proteins, and caspase 9. Given its diverse actions, compounds that suppress the PI3K/Akt pathway have potential pharmacologic utility as angiogenesis inhibitors and antineoplastic agents. Using the SVR angiogenesis assay, a screen of natural products, we isolated the alkaloid solenopsin, and found that it is a potent angiogenesis inhibitor. We also found that solenopsin inhibits the PI3K signaling pathway in cells upstream of PI3K, which may underlie its affects on angiogenesis. Consistent with inhibition of the activation of PI3K, solenopsin prevented only. For personal use at PENN STATE UNIVERSITY on February 21, 2013. bloodjournal.hematologylibrary.org From