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Anti-leukemic effects of the V-ATPase inhibitor Archazolid A.
Oncotarget 6, 43508-43528 (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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Archazolid ; Leukemia ; Natural Compounds; Acute Lymphoblastic-leukemia; Acute Myeloid-leukemia; Vacuolar H+-atpase; Chronic Lymphocytic-leukemia; Breast-cancer Cells; Therapeutic Target; Proton Pumps; Endoplasmic-reticulum; Drug-resistance; Notch Receptor
ISSN (print) / ISBN
1949-2553
e-ISSN
1949-2553
Journal
OncoTarget
Quellenangaben
Volume: 6,
Issue: 41,
Pages: 43508-43528
Publisher
Impact Journals LLC
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Gene Vector (AGV)