Techniques And Strategies For Wortmannin Who Few Know About

While previous studies have demonstrated that perifosine shows cytotoxic activity against different types of haematological malignancies, when used either alone or in combination with chemotherapeutic drugs http://www.selleckchem.com/products/CHIR-99021.html (van Blitterswijk & Verheij, 2008), its anti-leukaemic potential has not been investigated in combination with innovative compounds. Therefore, the effect of perifosine (Cayman Chemical, Ann Arbor, MI, USA) was analyzed in a panel of p53wild-type (SKW6.4, OCI, MOLM), p53mutated (BJAB, MAVER) and p53null (HL-60) cell lines, of both B lymphoid (SKW6.4, BJAB and MAVER) and myeloid (OCI, MOLM, HL-60) origin, all purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA) or obtained from DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Braunschweig, Germany). Perifosine was used alone or in combination with nutlin-3 (Cayman Chemical), a potent and selective small molecule inhibitor of the p53-MDM2 interaction, which induces a strong non genotoxic activation of the p53 pathway (Vassilev, 2007). In preliminary experiments, perifosine alone dose-dependently induced cytotoxicity, evaluated as previously described (Borgatti et?al, 1997), in all leukaemic cell lines. The simultaneous addition of high concentrations of perifosine plus nutlin-3 (10?��mol/l http://www.selleckchem.com/products/LY294002.html each) induced a significant (P? http://www.selleck.cn/products/wortmannin.html not in p53mutated BJAB and MAVER and p53null cell lines, with the exception of MAVER cell line at 24?h (Fig?1A). In order to evaluate whether the combined effect of perifosine plus nutlin-3 was synergistic, cultures were treated with serial concentrations of perifosine and nutlin-3 at a constant perifosine:nutlin-3 ratio, for 24 and 48?h and data were analyzed by the method of Chou and Talalay (1984). Synergy of perifosine plus nutlin-3 combination treatment (average combination index values