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EGCG inhibits recepteur d'origine nantais expression by suppressing Egr-1 in gastric cancer cells.
- Source :
-
International journal of oncology [Int J Oncol] 2013 Mar; Vol. 42 (3), pp. 1120-6. Date of Electronic Publication: 2013 Jan 16. - Publication Year :
- 2013
-
Abstract
- Abnormal accumulation and activation of the recepteur d'origine nantais (RON) has been implicated in epithelial tumor carcinogenesis. In the present study, we examined the effect of epigallocatechin-3-gallate (EGCG), the major green tea catechin, on the induction of RON and tumor growth in human gastric cancer. EGCG inhibited phorbol 12-myristate 13-acetate (PMA)-induced RON expression and reduced RON transcriptional activity. However, (-)-epigalloca-techin (EGC), (-)-epicatechin gallate (ECG) and (-)‑epicatechin (EC) did not affect RON expression. Experiments with deleted and site-directed mutagenesis of the RON promoter indicated that Egr-1 binding sites in the RON promoter may be the EGCG‑response element acting as a cis-element in gastric cancer cells. EGCG also inhibited PMA-induced Egr-1 expression and DNA binding in a dose-dependent manner. Furthermore, gastric cancer cells pretreated with PMA showed markedly enhanced invasiveness, which was partially abrogated by EGCG and siRNA-targeted RON and Egr-1. EGCG significantly reduced tumor growth in an in vivo tumor model, whereas RON expression was downregulated. These results suggest that EGCG may exert at least part of its anticancer effect by controlling RON expression through suppression of Egr-1 activation.
- Subjects :
- Animals
Catechin metabolism
Catechin pharmacology
Cell Line, Tumor
DNA-Binding Proteins antagonists & inhibitors
Early Growth Response Protein 1 antagonists & inhibitors
Early Growth Response Protein 1 genetics
Enzyme Activation
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Neoplasm Transplantation
Plant Extracts
Promoter Regions, Genetic
RNA Interference
RNA, Small Interfering
Receptor Protein-Tyrosine Kinases genetics
Tea
Tetradecanoylphorbol Acetate analogs & derivatives
Tetradecanoylphorbol Acetate pharmacology
Transcription, Genetic drug effects
Xenograft Model Antitumor Assays
Catechin analogs & derivatives
Early Growth Response Protein 1 metabolism
Receptor Protein-Tyrosine Kinases metabolism
Stomach Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2423
- Volume :
- 42
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 23337910
- Full Text :
- https://doi.org/10.3892/ijo.2013.1775