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Anti-leukemic effects of the V-ATPase inhibitor Archazolid A.
Zhang, Siwei Schneider, Lina S Vick, Binje Grunert, Michaela Jeremias, Irmela Menche, Dirk Vollmar, Angelika M Liebl, Johanna
Zhang, Siwei
Schneider, Lina S
Vick, Binje
Grunert, Michaela
Jeremias, Irmela
Menche, Dirk
Vollmar, Angelika M
Liebl, Johanna
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2015-12-22
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Abstract
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.
Citation
Anti-leukemic effects of the V-ATPase inhibitor Archazolid A. 2015, 6 (41):43508-28 Oncotarget
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en
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ISSN
1949-2553