Research Papers:

Anti-leukemic effects of the V-ATPase inhibitor Archazolid A

Siwei Zhang, Lina S. Schneider, Binje Vick, Michaela Grunert, Irmela Jeremias, Dirk Menche, Rolf Müller, Angelika M. Vollmar and Johanna Liebl _

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Oncotarget. 2015; 6:43508-43528. https://doi.org/10.18632/oncotarget.6180

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Siwei Zhang1, Lina S. Schneider1, Binje Vick2,4, Michaela Grunert2, Irmela Jeremias2,3,4, Dirk Menche5, Rolf Müller6, Angelika M. Vollmar1 and Johanna Liebl1

1 Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilians-University, Munich, Germany

2 Department of Gene Vectors, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany

3 Department of Oncology/Hematology, Dr. von Haunersches Kinderspital, Munich, Germany

4 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

5 Kekulé-Institut für Organische Chemie und Biochemie der Universität Bonn, Bonn, Germany

6 Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Centre for Infection Research and Department of Pharmaceutical Biotechnology, Saarland University, Saarbrücken, Germany

Correspondence to:

Johanna Liebl, email:

Keywords: Archazolid, leukemia, natural compounds

Received: May 20, 2015 Accepted: October 07, 2015 Published: October 19, 2015


Prognosis for patients suffering from T-ALL is still very poor and new strategies for T-ALL treatment are urgently needed. Our study shows potent anti-leukemic effects of the myxobacterial V-ATPase inhibitor Archazolid A. Archazolid A reduced growth and potently induced death of leukemic cell lines and human leukemic samples. By inhibiting lysosomal acidification, Archazolid A blocked activation of the Notch pathway, however, this was not the mechanism of V-ATPase inhibition relevant for cell death induction. In fact, V-ATPase inhibition by Archazolid A decreased the anti-apoptotic protein survivin. As underlying mode of action, this work is in line with recent studies from our group demonstrating that Archazolid A induced S-phase cell cycle arrest by interfering with the iron metabolism in leukemic cells. Our study provides evidence for V-ATPase inhibition as a potential new therapeutic option for T-ALL.

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