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

作者：Zhang Siwei; Schneider Lina S; Vick Binje; Grunert Michaela; Jeremias Irmela; Menche Dirk; Mueller Rolf; Vollmar Angelika M; Liebl Johanna

来源：Oncotarget, 2015, 6(41): 43508-43528.

DOI：10.18632/oncotarget.6180

• Archazolid
• leukemia
• natural compounds

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.

• 出版日期2015-12-22