Journal
FEBS LETTERS
Volume 582, Issue 29, Pages 4066-4076Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2008.11.001
Keywords
Cytotoxicity; Double-strand break; Cancer therapeutics; Chemotherapy; Callus; DNA damage
Funding
- Lady Tata Memorial Trust international award for leukemia research (London)
- DBT, India
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Methyl angolensate (MA), a natural tetranortriterpenoid, purified from Soymida febrifuga is examined for the first time for its anticancer properties. We find that MA inhibits growth of T-cell leukemia and chronic myelogenous leukemia cells in a time- and dose-dependent manner. Accumulation of cells in the subG1 peak, annexin V binding and DNA fragmentation suggested induction of apoptosis. Besides, upregulation of BAD (proapoptotic) and downregulation of BCL2 (antiapoptotic) gene products further supported induction of apoptosis. Loss of mitochondrial membrane potential, activation of caspase 9, caspase 3, cleavage of PARP, downregulation of Ku70/80 and phosphorylation of MAP kinases suggested that MA could induce intrinsic pathway of apoptosis in leukemic cells. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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