Linked Life Data

15769601

Source:http://linkedlifedata.com/resource/pubmed/id/15769601

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2005-3-16
pubmed:abstractText
It has been suggested that proteasome activity is essential for tumor cell proliferation and drug resistance development. We have previously shown that natural and synthetic ester bond-containing tea polyphenols are selective inhibitors of the chymotrypsin-like activity of the proteasome. The most abundant catechin in green tea is (-)-epigallocatechin-3-gallate [(-)-EGCG], which has been found by many laboratories to exhibit the most potent anticancer activity. We have reported that (-)-EGCG is also the most effective proteasome inhibitor among all the natural green tea catechins tested. Unfortunately, (-)-EGCG is very unstable in neutral and alkaline conditions. In an attempt to increase the stability and thus the efficacy, we synthesized several (-)-EGCG analogs with acetyl protected -OH groups as prodrugs. Here we report, for the first time, that these acetylated synthetic tea analogs are much more potent than natural (-)-EGCG in inhibiting the proteasome in cultured tumor cells. Consistently, these protected analogs showed much higher potency than (-)-EGCG to inhibit proliferation and transforming activity and to induce apoptosis in human leukemic, prostate, breast, and simian virus 40-transformed cells. Additionally, these protected analogs had greatly reduced effects on human normal and non-transformed cells. Therefore, these peracetate protected tea polyphenols are more efficacious than (-)-EGCG and possess great potential to be developed into novel anticancer drugs. Identification of the cytosolic metabolite(s) of peracetate-protected polyphenols in cultured tumor cells and examination of their in vivo tumor growth-inhibitory activity are currently underway in our laboratory.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1093-4715
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1010-23
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Synthetic peracetate tea polyphenols as potent proteasome inhibitors and apoptosis inducers in human cancer cells.
pubmed:affiliation
The Prevention Program, Barbara Ann Karmanos Cancer Institute and Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't