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

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.

SUBMITTER: Zhang S

PROVIDER: S-EPMC4791247 | biostudies-other | 2015 Dec

REPOSITORIES: biostudies-other

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

Zhang Siwei S Schneider Lina S LS Vick Binje B Grunert Michaela M Jeremias Irmela I Menche Dirk D Müller Rolf R Vollmar Angelika M AM Liebl Johanna J

Oncotarget 20151201 41

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 de ...[more]

PMID: 26496038

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