Methyl angolensate, a natural tetranortriterpenoid induces intrinsic apoptotic pathway in leukemic cells.
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.
Chiruvella
Kishore K
KK
Department of Biochemistry, Indian Institute of Science, Malleswaram, Bangalore 560 012, Karnataka, India.
Kari
Vijayalakshmi
V
Choudhary
Bibha
B
Nambiar
Mridula
M
Ghanta
Rama Gopal
RG
Raghavan
Sathees C
SC
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
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