NAG-1 up-regulation mediated by EGR-1 and p53 is critical for quercetin-induced apoptosis in HCT116 colon carcinoma cells
- J. H. Lim; J.-W. Park; D. S. Min; J.-S. Chang; Y. H. Lee; Y. B. Park; K. S. Choi; T. K. Kwon
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- 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-β superfamily protein, during quercetininduced
apoptosis of HCT116 human colon carcinoma cells.
Reporter assays using the luciferase constructs contain-ing NAG-1 promoter region demonstrate that early growth
response-1 (EGR-1) and p53 are required for quercetinmediated
activation of the NAG-1 promoter. Overexpression
ofNAG-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.
Keywords Quercetin . NAG-1 . Apoptosis . Sp1 . EGR-1 .
p53 . Colon carcinoma cells
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