Molecular Nutrition & Food Research · 2007 · 38 citations · 30 references
Life SciencesOncologyPharmacologyApoptosisCancer PharmacologyMolecular OncologyApoptosis In CancerApoptosis RegulationApoptotic SignalingBcl-2 Family ProteinsIntrinsic Apoptotic PathwayReactive Oxygen SpeciesAnticancer ActivityApoptosis Regulation By KinasesApoptosis Signaling In CancerApoptotic Signaling In CancerCytochrome C-mediated Caspase ActivationReactive Oxygen Species GenerationReactive Oxygen Species-induced ApoptosisReactive Oxygen Species-mediated Apoptosis
1,6-O,O-diacetylbritannilactone (OODBL) isolated from Inula britannica, exhibits potent antitumor activity against several human cancer cell lines. However, the molecular mechanism of OODBL in the induction of anticancer activity is still unclear. In the present study, we demonstrated that OODBL induced the occurrence of apoptosis in human leukemic (HL-60) cells and cell arrest at the S phase. On the other hand, activation of caspase-8, -9, and -3, phosphorylation of Bcl-2 and Bid, and increased release of cytochrome c from mitochondria into cytosolic fraction were detected in OODBL-treated HL-60 cells. We further demonstrated that production of reactive oxygen species (ROS), activation of mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) signaling pathways may play an important role in OODBL-induced apoptosis. The results from the present study highlight the molecular mechanisms underlying OODBL-induced anticancer activity.
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