Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 276, Issue 16, Pages 13322-13330Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M004209200
Keywords
-
Categories
Ask authors/readers for more resources
It has been discovered that proteasome inhibitors are able to induce tumor growth arrest or cell death and that tea consumption is correlated with cancer prevention. Here, we show that ester bond-containing tea polyphenols, such as (-)-epigallocatechin-3-gallate (EGCG), potently and specifically inhibit the chymotrypsin-like activity of the proteasome in vitro (IC50 = 86-194 nM) and in vivo (1-10 muM) at the concentrations found in the serum of green tea drinkers. Atomic orbital energy analyses and high performance liquid chromatography suggest that the carbon of the polyphenol ester bond is essential for targeting, thereby inhibiting the proteasome in cancer cells. This inhibition of the proteasome by EGCG in several tumor and transformed cell lines results in the accumulation of two natural proteasome substrates, p27(Kip1) and I kappaB-alpha, an inhibitor of transcription factor NF-kappaB, followed by growth arrest in the G, phase of the cell cycle. Furthermore, compared with their simian virus-transformed counterpart, the parental normal human fibroblasts were much more resistant to EGCG-induced p27(Kip1) protein accumulation and G(1) arrest. Our study suggests that the proteasome is a cancer-related molecular target of tea polyphenols and that inhibition of the proteasome activity by ester bond containing polyphenols may contribute to the cancer-preventative effect of tea.
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