[Effect of NF-kappaB on inhibition of non-small cell lung cancer cell cyclooxygenase-2 by brucine].
OBJECTIVE
To study the molecular mechanism of cyclooxygenase-2 (COX-2), one of effective ingredient of brucine, in inducing non-small cell lung cancer cell apoptosis.


METHODS
COX-2 promoter, transcription factor deletion mutants and COX-2 mRNA 3'-UTR-containing report plasmids were transfected with Renillia to non-small cell lung cancer A549 cell, in order to detect the activity of report gene luciferase and minimum cis-acting element of COX-2 promoter inhibited by brucine. The influence of brucine on IkappaB phosphorylation and the nuclear translocation of p65 were detected by immunoblotting assay.


RESULTS
Brucine significantly suppressed LPS-induced COX-2 promoter activation, but revealed minor impact on COX-2 mRNA stability. NF-kappaB in the vicinity of COX-2 promoter-262 was an important cis-acting element of brucine for inhibiting the activity of COX-2 promoter. Brucine was found to inhibit the phosphorylation of IkappaBalpha as well as the nuclear translocation of p65.


CONCLUSIONS
Brucine can improve A549 cells apoptosis by inhibiting the activity of NF-kappaB and the subsequent COX-2 gene expression.
Department of Medical Examination, Gaochun Hospital of Nanjing, Nanjing 211300, China.
Guomin
G
Zhu
Fangzhou
F
Yin
Xukun
X
Deng
D001692:Biological Transport / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D020871:RNA Stability / Q000187:drug effects; D013331:Strychnine / Q000031:analogs & derivatives* / Q000494:pharmacology
D016328:NF-kappa B; C083806:brucine; D051546:Cyclooxygenase 2; D013331:Strychnine