title: Methyl angolensate, a natural tetranortriterpenoid induces intrinsic apoptotic pathway in leukemic cells.
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.
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Malleswaram, Bangalore 560 012, Karnataka, India.
authors.forename: Kishore K
authors.initials: KK
authors.lastname: Chiruvella
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Kari
authors.forename: Bibha
authors.initials: B
authors.lastname: Choudhary
authors.forename: Mridula
authors.initials: M
authors.lastname: Nambiar
authors.forename: Rama Gopal
authors.initials: RG
authors.lastname: Ghanta
authors.forename: Sathees C
authors.initials: SC
authors.lastname: Raghavan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D024161:Collagen Type XI / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D015458:Leukemia, T-Cell / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D051025:bcl-Associated Death Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494819:BAD protein, human; C499319:COL11A2 protein, human; D024161:Collagen Type XI; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; D051025:bcl-Associated Death Protein; C092741:methyl angolensate; D053181:Caspase 8; D053453:Caspase 9