PT  - JOURNAL ARTICLE
AU  - JEONG-AH KIM
AU  - EDWARD K. LAU
AU  - LI PAN
AU  - ESPERANZA J. CARCACHE DE BLANCO
TI  - NF-κB Inhibitors from <em>Brucea javanica</em> Exhibiting Intracellular Effects on Reactive Oxygen Species
DP  - 2010 Sep 01
TA  - Anticancer Research
PG  - 3295--3300
VI  - 30
IP  - 9
4099  - http://ar.iiarjournals.org/content/30/9/3295.short
4100  - http://ar.iiarjournals.org/content/30/9/3295.full
SO  - Anticancer Res2010 Sep 01; 30
AB  - 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.