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Schneider, Lina S
Vollmar, Angelika M
MetadataShow full item record
AbstractPrognosis 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.
CitationAnti-leukemic effects of the V-ATPase inhibitor Archazolid A. 2015, 6 (41):43508-28 Oncotarget
AffiliationHelmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland 9 University, 66123 Saarbrücken, Germany.
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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- V-ATPase inhibition by archazolid leads to lysosomal dysfunction resulting in impaired cathepsin B activation in vivo.
- Authors: Kubisch R, Fröhlich T, Arnold GJ, Schreiner L, von Schwarzenberg K, Roidl A, Vollmar AM, Wagner E
- Issue date: 2014 May 15
- The V-ATPase-inhibitor archazolid abrogates tumor metastasis via inhibition of endocytic activation of the Rho-GTPase Rac1.
- Authors: Wiedmann RM, von Schwarzenberg K, Palamidessi A, Schreiner L, Kubisch R, Liebl J, Schempp C, Trauner D, Vereb G, Zahler S, Wagner E, Müller R, Scita G, Vollmar AM
- Issue date: 2012 Nov 15
- Vacuolar-ATPase Inhibition Blocks Iron Metabolism to Mediate Therapeutic Effects in Breast Cancer.
- Authors: Schneider LS, von Schwarzenberg K, Lehr T, Ulrich M, Kubisch-Dohmen R, Liebl J, Trauner D, Menche D, Vollmar AM
- Issue date: 2015 Jul 15
- Inhibition of the V-ATPase by Archazolid A: A New Strategy to Inhibit EMT.
- Authors: Merk H, Messer P, Ardelt MA, Lamb DC, Zahler S, Müller R, Vollmar AM, Pachmayr J
- Issue date: 2017 Nov
- Resistance mechanisms of cancer cells to the novel vacuolar H(+)-ATPase inhibitor archazolid B.
- Authors: Hamm R, Sugimoto Y, Steinmetz H, Efferth T
- Issue date: 2014 Oct