부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.bcp.2006.06.015 Byline: Michal Hayun (a), Yaniv Naor (a), Merav Weil (a), Michael Albeck (b), Alpha Peled (c), Jeremy Don (a), Nechama Haran-Ghera (c), Benjamin Sredni (a) Keywords: AS101; Multiple Myeloma; Survivin; Akt; Apoptosis; Caspases Abbreviations: Cdk, cyclin-dependent kinase; IAPs, inhibitors of apoptosis proteins; IGF-1, insulin-like growth factor 1; MM, Multiple Myeloma; PI, propidium iodide; PI3-K, phosphatidylinositol-3-OH kinase Abstract: Multiple Myeloma (MM) is a clonal B-cell malignancy affecting both the immune and the skeletal systems, and accounts for 10% of all hematological cancers. The immunomodulator ammonium trichloro (dioxoethylene-O,O') tellurate (AS101) is a non-toxic compound which has direct anti-tumoral properties in several tumor models. The present study examined the anti-tumoral activity of AS101 in MM by targeting the Akt/Survivin signaling pathway, crucial for survival. We showed that AS101 inhibites cell proliferation and colonies formation of MM cell lines, in a dose-dependent manner. AS101 induced G.sub.2/M growth arrest and increased both cyclin-dependent kinase inhibitor p21.sup.waf1 protein levels and Cdk1 (p34.sup.cdc2) -- inhibitory phosphorylation. Longer incubation of MM cells with AS101 resulted in accumulation of apoptotic cell population and in increased caspase 9, 3 and 7 activities. We also showed that AS101 down-regulated Akt phosphorylation and decreased expression of the inhibitor of apoptosis, survivin. Since Akt and survivin are potentials targets for MM therapy, we suggest that AS101, currently being used in clinical studies, may have therapeutic implications in myeloma and other hematopoietic malignancies. Author Affiliation: (a) Safdie Institute for AIDS and Immunology Research, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel (b) Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel (c) Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel Article History: Received 30 April 2006; Accepted 13 June 2006