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NAG-1 up-regulation mediated by EGR-1 and p53 is critical for quercetin-induced apoptosis in HCT116 colon carcinoma cells.

Authors
Lim, JH; Park, JW; Min, DS; Chang, JS; Lee, YH; Park, YB; Choi, KS; Kwon, TK
Citation
Apoptosis : an international journal on programmed cell death, 12(2):411-421, 2007
Journal Title
Apoptosis : an international journal on programmed cell death
ISSN
1360-81851573-675X
Abstract
Quercetin, a flavonoid molecule ubiquitously present in nature, has multiple effects on cancer cells, including the inhibition of cell proliferation and migration. However, the responsible molecular mechanisms are not fully understood. We found that quercetin induces the expression of NAG-1 (Non-steroidal anti-inflammatory drug activated gene-1), a TGF-beta superfamily protein, during quercetin-induced apoptosis of HCT116 human colon carcinoma cells. Reporter assays using the luciferase constructs containing NAG-1 promoter region demonstrate that early growth response-1 (EGR-1) and p53 are required for quercetin-mediated activation of the NAG-1 promoter. Overexpression of NAG-1 enhanced the apoptotic effect of quercetin, but suppression of quercetin-induced NAG-1 expression by NAG-1 siRNA attenuated quercetin-induced apoptosis in HCT116 cells. Taken together, the present study demonstrates for the first time that quercetin induces apoptosis via NAG-1, providing a mechanistic basis for the apoptotic effect of quercetin in colon carcinoma cells.
MeSH terms
Apoptosis/drug effects*Base SequenceBinding Sites/drug effectsColonic Neoplasms/geneticsColonic Neoplasms/pathology*Cytokines/genetics*Cytokines/metabolismDose-Response Relationship, DrugEarly Growth Response Protein 1/metabolism*Gene Expression Regulation, Neoplastic/drug effectsGrowth Differentiation Factor 15HCT116 CellsHT29 CellsHumansMolecular Sequence DataPromoter Regions, Genetic/drug effectsPromoter Regions, Genetic/geneticsQuercetin/pharmacology*RNA, Messenger/geneticsRNA, Messenger/metabolismSp1 Transcription Factor/metabolismTranscriptional Activation/drug effectsTumor Suppressor Protein p53/metabolism*Up-Regulation/drug effects*
DOI
10.1007/s10495-006-0576-9
PMID
17191121
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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