Gastroenterology

Gastroenterology

Volume 134, Issue 7, June 2008, Pages 1972-1980
Gastroenterology

Basic–Alimentary Tract
A Green Tea Component Suppresses Posttranslational Expression of Basic Fibroblast Growth Factor in Colorectal Cancer

https://doi.org/10.1053/j.gastro.2008.02.095Get rights and content

Background & Aims: Green tea catechins are known to have anticarcinogenic effects. Epigallocatechin-3-gallate (EGCG) accounts for almost 50% of the total catechin content in green tea extract and has very potent antioxidant effects. EGCG also inhibits angiogenesis, possibly through the inhibition of proangiogenic factors including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which in turn, inhibits tumor growth and metastasis. However, the exact molecular mechanism by which EGCG suppresses bFGF expression is not known. Our objective was to elucidate the molecular mechanisms by which EGCG inhibits bFGF expression in colorectal cancer. Methods: We examined posttranslational regulation of bFGF by EGCG in human colorectal cancer cells. We also examined bFGF in intestinal tumor formation of APCMin/+ mice with and without catechin treatment. Results: The bFGF protein was quickly degraded in the presence of EGCG, but a proteasome inhibitor suppressed this degradation. EGCG was also found to increase ubiquitination of bFGF and trypsin-like activity of the 20S proteasome, thereby resulting in the degradation of bFGF protein. Furthermore, EGCG suppressed tumor formation in APCMin/+ mice, compared with vehicle-treated mice, in association with reduced bFGF expression. Conclusions: The ubiquitin-proteasome degradation pathway contributes significantly to down-regulation of bFGF expression by EGCG. Catechin compounds have fewer adverse effects than chemotherapeutic agents and hence can be used as proof-of-concept in cancer therapeutics to suppress growth and metastasis by targeting proteins such as bFGF.

Section snippets

Cell Culture and Reagents

All cell lines were purchased from the American Type Culture Collection (Manassas, VA), except the head and neck cancer cell line, SPCCY-1, which was obtained from Dr Dong M. Shin (Emory University, Atlanta, GA). All chemicals were purchased from Fischer Scientific (Pittsburgh, PA), unless otherwise specified. Primary antibodies for bFGF and β-catenin were purchased from BD Transduction Laboratories (San Jose, CA). VEGF and actin primary antibodies were obtained from Santa Cruz Biotechnology,

Basic FGF Suppression by Green Tea Catechins

Although extensive research has focused on the mechanisms involved in how EGCG affects VEGF suppression,14, 15 little attention has been given to the suppression mechanism of EGCG on bFGF expression. To address this, we examined 4 human colorectal cell lines and found that only 2 cell lines, HCT-116 and LoVo, expressed bFGF. LoVo cells highly expressed bFGF protein, whereas HCT-116 cells marginally expressed bFGF. Notable bFGF was detected as 2 bands (18 and 24 kilodaltons), and EGCG treatment

Discussion

Green tea acts as an anticancer agent, especially in colon cancer. Although the molecular mechanism of this anticancer effect is still not entirely understood, most green tea effects are believed to result from EGCG.23 In addition to its chemopreventive activity, EGCG is known to possess antiangiogenic properties through inhibition of proangiogenic factors including VEGF and bFGF.24, 25 Our results show that EGCG suppresses the protein levels of bFGF and VEGF in colorectal cancer cells, which

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    Supported primarily by NIH grant R21CA109423 (to S.J.B.) and K26RR016645 (to M.F.M.).

    Conflicts of interest: No conflicts of interest exist.

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