Document Detail


Epigallocatechin-3 gallate induces growth inhibition and apoptosis in human breast cancer cells through survivin suppression.
MedLine Citation:
PMID:  17786300     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent investigations have demonstrated that polyphenolic catechins inhibit cancer cell proliferation and tumor growth. However, how the major active component of tea catechins, epigallocatechin-3 gallate (EGCG), mediates anticancerous effects has not been extensively examined. We have investigated the cell growth inhibitory effects of EGCG on cell growth of the human breast cancer cell line MCF-7, and the mechanism of its action with emphasis on the regulation of tumor cell survival. A significant EGCG dose-dependent growth inhibition was observed coordinated with EGCG-induced apoptosis. Analysis of survivin expression after addition of EGCG showed that both survivin mRNA and protein were decreased. The survivin-promoter luciferase activity in EGCG-treated cells was significantly inhibited by 91+/-2.0% (P<0.001), compared with the control. Interestingly, EGCG strongly inhibited the basal activation of phospho-AKT and AKT kinase activity as early as 30 min after treatment. Furthermore, inhibition of AKT kinase activity by EGCG preceded the suppression of survivin (1 h post treatment), followed by increased caspase-9 activity (6 h post treatment). A dominant negative AKT or the phosphatidylinositol 3-kinase inhibitor, LY294002, also strongly inhibited survivin promoter activity, providing further evidence to support the hypothesis that the inhibitory effect of EGCG on survivin is mediated via the AKT pathway. Therefore, EGCG is a potent proapoptotic agent in MCF-7 breast cancer cells that targets survivin expression via suppression of the AKT pathway.
Authors:
Yan Tang; Daniel Y Zhao; Steven Elliott; Weiqiang Zhao; Tyler J Curiel; Barbara S Beckman; Matthew E Burow
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of oncology     Volume:  31     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-05     Completed Date:  2007-11-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  705-11     Citation Subset:  IM    
Affiliation:
Department of Medicine, Section of Hematology and Medical Oncology, Center for Bioenvironmental Research, Tulane Cancer Center, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism
Anticarcinogenic Agents / pharmacology*
Apoptosis / drug effects*
Blotting, Western
Breast Neoplasms / drug therapy,  metabolism,  pathology*
Catechin / analogs & derivatives*,  pharmacology
Cell Line, Tumor
Colony-Forming Units Assay
Gene Expression Regulation, Neoplastic*
Humans
Luciferases / metabolism
Microtubule-Associated Proteins / antagonists & inhibitors*,  metabolism
Neoplasm Proteins / antagonists & inhibitors*,  metabolism
Promoter Regions, Genetic
Protease Inhibitors / pharmacology
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction
Chemical
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/BIRC5 protein, human; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; 0/Protease Inhibitors; 154-23-4/Catechin; 989-51-5/epigallocatechin gallate; EC 1.13.12.-/Luciferases; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

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