NF-kappaB inhibitors from Brucea javanica exhibiting intracellular effects on reactive oxygen species.

Abstract:

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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Kim JA,Lau EK,Pan L,De Blanco EJ

subject

Has Abstract

pub_date

2010-09-01 00:00:00

pages

3295-300

issue

9

eissn

0250-7005

issn

1791-7530

pii

30/9/3295

journal_volume

30

pub_type

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