AIM: Brucea javanica was studied to identify nuclear factor kappaB (NF-κB) inhibitors exhibiting reactive oxygen species (ROS) intracellular amplification. MATERIAL AND METHODS: Eight compounds were evaluated for selective cytotoxicity using HT-29, HeLa, and HL-60 cells, and in a NF-κB assay. Active compounds were then tested using ROS and mitochondria transmembrane potential (MTP) assays. NF-κB and nuclear factor activated T-cell (NFAT) translocation were also assessed using their respective whole cell assays. RESULTS: Bruceajavanone B, bruceantin, bruceine A, (-)-hydnocarpin, and chrysoeriol exhibited cytotoxic potential and NF-κB p65 inhibition. Chrysoeriol exhibited selective cytotoxicity against leukemia cells with greater potency and also showed an ability to up-regulate NFAT transcriptional pathways through the amplification of intracellular ROS, in the presence of H2O2, to a greater degree than bruceantin and bruceine. CONCLUSION: Chrysoeriol selectively kills leukemic cells and potentiates the amplification of ROS levels. Therefore, chrysoeriol could serve as a potential chemotherapeutic modifier for leukemia chemotherapy since leukemia cells have a higher susceptibility to elevated ROS levels.
AIM: Brucea javanica was studied to identify nuclear factor kappaB (NF-κB) inhibitors exhibiting reactive oxygen species (ROS) intracellular amplification. MATERIAL AND METHODS: Eight compounds were evaluated for selective cytotoxicity using HT-29, HeLa, and HL-60 cells, and in a NF-κB assay. Active compounds were then tested using ROS and mitochondria transmembrane potential (MTP) assays. NF-κB and nuclear factor activated T-cell (NFAT) translocation were also assessed using their respective whole cell assays. RESULTS:Bruceajavanone B, bruceantin, bruceine A, (-)-hydnocarpin, and chrysoeriol exhibited cytotoxic potential and NF-κB p65 inhibition. Chrysoeriol exhibited selective cytotoxicity against leukemia cells with greater potency and also showed an ability to up-regulate NFAT transcriptional pathways through the amplification of intracellular ROS, in the presence of H2O2, to a greater degree than bruceantin and bruceine. CONCLUSION:Chrysoeriol selectively kills leukemic cells and potentiates the amplification of ROS levels. Therefore, chrysoeriol could serve as a potential chemotherapeutic modifier for leukemia chemotherapy since leukemia cells have a higher susceptibility to elevated ROS levels.
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