Journal
GASTROENTEROLOGY
Volume 134, Issue 7, Pages 1972-1980Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2008.02.095
Keywords
-
Categories
Funding
- NCI NIH HHS [R21 CA109423-02, R21 CA109423-01A1, R21 CA109423, R21CA109423] Funding Source: Medline
- NCRR NIH HHS [K26 RR016645, K26RR016645] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R21CA109423] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [K26RR016645] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [ZIAES010016] Funding Source: NIH RePORTER
Ask authors/readers for more resources
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 APC(Min)/(+) 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 APC(Min)/(+) 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. Cat echin 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available