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Effect of (−)‐epigallocatechin gallate on cyclin D1 down‐regulation at the post‐translational level
Author(s) -
Zhang Xiaobo,
Baek Seung Joon
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.366.7
Subject(s) - cyclin d1 , cyclin b , cancer research , cyclin d , cyclin , chemistry , cyclin a2 , cell cycle , cyclin a , microbiology and biotechnology , biology , apoptosis , biochemistry
The potential anti‐carcinogenic effect of green tea catechins has been well documented, especially for one of the major components, (−)‐epigallocatechin gallate (EGCG). Cyclin D1, an oncogenic protein, has been shown to be up‐regulated in various cancer cells, including colorectal cancer. It has been reported that EGCG inhibited cyclin D1 at the transcriptional and translational levels; however, the detailed mechanisms by which EGCG suppresses cyclin D1 expression have not been elucidated. Our objective was to elucidate the molecular mechanism(s) and biological consequence of EGCG‐induced cyclin D1 down‐regulation in colorectal cancer cells. We examined the effect of EGCG on the expression of cell growth related proteins in colorectal cancer cells. As a result, we found that EGCG inhibited cell growth and induced cell cycle arrest and apoptosis. The expression of cylin D1 and D3, but not cyclin E was down‐regulated, while p21 was up‐regulated in the presence of EGCG. Moreover, the cyclin D1 down‐regulation by EGCG was mediated by the 26S proteasome pathway dependent of glycogen synthase kinase‐3 beta (GSK‐3β). Collectively, EGCG facilitates the proteasomal degradation of cyclin D1, which could, at least in part, be responsible for the anti‐cancer effect of EGCG in colorectal cancer. Supported by: NIH R01CA108975 and The University of Tennessee Center of Excellence in Livestock Diseases and Human Health grantGrant Funding Source : NIH R01CA108975