Poster No. 52 Archazolid B, a New V-ATPase-Inhibitor of Myxobacterial Origin, Exhibits Anti-Metastatic Potential Romina Wiedmann 1 , Ingrid Chen2, Dirk Trauner2, Anita Rudy1, Angelika M. Vollmar1 1 Department of Pharmacy, Center for Drug Research, Pharmaceutical Biology, Ludwig-Maximilians-University, Munich, Munich,

Germany, 2 Department of Chemistry and Biochemistry, Ludwig-Maximilians-University, Munich, Munich, Germany Resistance of chemotherapy and the rapid formation of metastasis are the main problems in the treatment of highly invasive cancers. Growing evidence suggests that V-ATPase, which is highly overexpressed in metastatic cancer cells, contributes A-1210477 to an acidic tumor environment, promoting cancer progression and metastasis. Archazolid B is a V-ATPase-inhibitor, isolated originally from the myxobacterium Archangium gephyra. We therefore hypothesize that Archazolid B could be a potent compound to inhibit the metastatic process in highly invasive cancer cells and to overcome chemoresistance by www.selleckchem.com/products/XAV-939.html directly regulating the pH gradient within the tumor microenvironment. We could show that Archazolid B changes the intra-and extracellular pH of tumor cells and potently inhibits the proliferation of highly

metastatic cancer cells (L3.6pl: IC50 ~ 80 pM; SK-BR-3: IC50 ~ 500 selleck kinase inhibitor pM). Interestingly, Archazolid B has only a moderate apoptotic effect (about 20 % apoptosis at 1 nM, 48 h) accompanied by the activation of Caspase 8 and 9 and the downregulation of anti-apoptotic proteins. Along with a strong inhibition of the clonogenic tumor cell growth, our most recent data shows that Archazolid B potently inhibits the migration of highly metastatic cancer cells. Taken together, Archazolid

B inhibits the growth and survival of highly proliferating cancer cells as well as their migration. Ongoing experiments will investigate molecular mechanisms and targets involved other than V-ATPase. Since V-ATPase, targeted by Archazolid B, controls the cancer microenvironment this experimental drug opens tuclazepam up the opportunity to increase the efficiency of different chemotherapeutics and therefore to overcome drug resistance of highly invasive cancer cells. Poster No. 53 Kynurenine Induce Tolerogenic Dendritic Cell Maturation Claudia Zavadil 1 , Michael Unger1, Marina Pargger1, Markus Stoeger1, Karin Joehrer1, Richard Greil2, Raimund Margreiter1, Albert Amberger1 1 Gastrointestinal Unit, Tyrolean Cancer Research Institute, Innsbruck, Austria, 2 III Medical Department, Private Medical University Hospital, Salzburg, Austria In the progression of cancer, malignant cells evolve strategies to avoid an immune response probably through induction of immune tolerance. It is proposed that dendritic cells (DC) have a dramatic impact on tumor immune tolerance and that the tumor microenvironment determine differentiation of DC into a tolerogenic phenotype.