Methyl angolensate, a natural tetranortriterpenoid induces intrinsic apoptotic pathway in leukemic cells |
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Authors: | Kishore K. Chiruvella Bibha Choudhary Rama Gopal Ghanta |
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Affiliation: | a Department of Biochemistry, Indian Institute of Science, Malleswaram, Bangalore 560 012, Karnataka, India b Manipal Institute of Regenerative Medicine, Manipal University, Bangalore 560 071, Karnataka, India c Division of Plant Tissue Culture, Sri Venkateswara University, Tirupati, AP, India |
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Abstract: | 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. |
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Keywords: | Cytotoxicity Double-strand break Cancer therapeutics Chemotherapy Callus DNA damage |
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