title: A natural compound, methyl angolensate, induces mitochondrial pathway of apoptosis in Daudi cells.
abstract: Natural products discovered from medicinal plants have played an important role in the treatment of cancer. In an effort to identify novel small molecules which can affect the proliferation of lymphoma cells, we tested methyl angolensate (MA), a plant derived tetranortriterpenoid, purified from the crude extract of the root callus of Soymida febrifuga commonly known as Indian red wood tree. We have tested MA for its cytotoxic properties on Burkitt's lymphoma cell lines, using various cellular assays. We observed that MA induces cytotoxicity in Daudi cells in a dose-dependent manner using trypan blue, MTT and LDH assays. We find that the treatment with MA led to activation of DNA double-strand break repair proteins including KU70 and KU80, suggesting the activation of nonhomologous DNA end joining pathway in surviving cells. Further, we find that methyl angolensate could induce apoptosis by cell cycle analysis, annexin V-FITC staining, DNA fragmentation and PARP cleavage. Besides, MA treatment led to reactive oxygen species generation and loss of mitochondrial transmembrane potential. These results suggest the activation of mitochondrial pathway of apoptosis. Hence, we identify MA as a potential chemotherapeutic agent against Daudi cells.
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore, 560 012, India.
authors.forename: Kishore K
authors.initials: KK
authors.lastname: Chiruvella
authors.forename: Sathees C
authors.initials: SC
authors.lastname: Raghavan
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001688:Biological Products / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D045643:DNA Repair Enzymes / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011419:Propidium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017304:Annexin A5; D001688:Biological Products; D017382:Reactive Oxygen Species; D014315:Triterpenes; C092741:methyl angolensate; D011419:Propidium; D045643:DNA Repair Enzymes