Effect of NF-kappaB on inhibition of non-small cell lung cancer cell cyclooxygenase-2 by brucine.
- Author:
Guomin ZHU
1
;
Fangzhou YIN
;
Xukun DENG
Author Information
- Publication Type:Journal Article
- MeSH: Biological Transport; drug effects; Carcinoma, Non-Small-Cell Lung; genetics; metabolism; Cell Line, Tumor; Cyclooxygenase 2; genetics; Humans; NF-kappa B; metabolism; Phosphorylation; drug effects; Promoter Regions, Genetic; drug effects; genetics; RNA Stability; drug effects; Strychnine; analogs & derivatives; pharmacology
- From: China Journal of Chinese Materia Medica 2012;37(9):1269-1273
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the molecular mechanism of cyclooxygenase-2 (COX-2), one of effective ingredient of brucine, in inducing non-small cell lung cancer cell apoptosis.
METHODCOX-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.
RESULTBrucine 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.
CONCLUSIONBrucine can improve A549 cells apoptosis by inhibiting the activity of NF-kappaB and the subsequent COX-2 gene expression.
