Document Detail


NF-kappaB inhibitors from Brucea javanica exhibiting intracellular effects on reactive oxygen species.
MedLine Citation:
PMID:  20944100     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jeong-Ah Kim; Edward K Lau; Li Pan; Esperanza J Carcache De Blanco
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Anticancer research     Volume:  30     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-10-14     Completed Date:  2010-11-10     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  3295-300     Citation Subset:  IM    
Affiliation:
Division of Pharmacy Practice and Administration, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
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MeSH Terms
Descriptor/Qualifier:
Brucea / chemistry*
Cell Line, Tumor
Flavonoids / pharmacology
Flavonolignans / pharmacology
Humans
Membrane Potential, Mitochondrial / drug effects
NF-kappa B / antagonists & inhibitors*,  metabolism
NFATC Transcription Factors / drug effects,  metabolism
Plant Extracts / pharmacology*
Quassins / pharmacology
Reactive Oxygen Species / metabolism*
Triterpenes / pharmacology
Grant Support
ID/Acronym/Agency:
P01 CA125066-03/CA/NCI NIH HHS; P01-CA125066/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Flavonoids; 0/Flavonolignans; 0/NF-kappa B; 0/NFATC Transcription Factors; 0/Plant Extracts; 0/Quassins; 0/Reactive Oxygen Species; 0/Triterpenes; 161043-67-0/bruceajavanin B; 25514-31-2/bruceine A; 41451-75-6/bruceantin; 491-71-4/chrysoeriol; 51419-48-8/hydnocarpin
Comments/Corrections

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