PMID- 21300025
OWN - NLM
STAT- MEDLINE
DCOM- 20110505
LR  - 20211203
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 406
IP  - 2
DP  - 2011 Mar 11
TI  - Epigallocatechin gallate (EGCG), a major component of green tea, is a dual 
      phosphoinositide-3-kinase/mTOR inhibitor.
PG  - 194-9
LID - 10.1016/j.bbrc.2011.02.010 [doi]
AB  - The PI3K signaling pathway is activated in a broad spectrum of human cancers, 
      either directly by genetic mutation or indirectly via activation of receptor 
      tyrosine kinases or inactivation of the PTEN tumor suppressor. The key nodes of 
      this pathway have emerged as important therapeutic targets for the treatment of 
      cancer. In this study, we show that (-)-epigallocatechin-3-gallate (EGCG), a 
      major component of green tea, is an ATP-competitive inhibitor of both 
      phosphoinositide-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) with 
      K(i) values of 380 and 320nM respectively. The potency of EGCG against PI3K and 
      mTOR is within physiologically relevant concentrations. In addition, EGCG 
      inhibits cell proliferation and AKT phosphorylation at Ser473 in MDA-MB-231 and 
      A549 cells. Molecular docking studies show that EGCG binds well to the PI3K 
      kinase domain active site, agreeing with the finding that EGCG competes for ATP 
      binding. Our results suggest another important molecular mechanism for the 
      anticancer activities of EGCG.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Van Aller, Glenn S
AU  - Van Aller GS
AD  - Department of Cancer Research, GlaxoSmithKline, Collegeville, PA 19426, USA. 
      glenn.s.van.aller@gsk.com
FAU - Carson, Jeff D
AU  - Carson JD
FAU - Tang, Wei
AU  - Tang W
FAU - Peng, Hao
AU  - Peng H
FAU - Zhao, Lin
AU  - Zhao L
FAU - Copeland, Robert A
AU  - Copeland RA
FAU - Tummino, Peter J
AU  - Tummino PJ
FAU - Luo, Lusong
AU  - Luo L
LA  - eng
PT  - Journal Article
DEP - 20110215
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Tea)
RN  - 8R1V1STN48 (Catechin)
RN  - BQM438CTEL (epigallocatechin gallate)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Catechin/*analogs & derivatives/chemistry/metabolism/pharmacology
MH  - Cell Proliferation/drug effects
MH  - HEK293 Cells
MH  - Humans
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation/drug effects
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Tea/*chemistry
EDAT- 2011/02/09 06:00
MHDA- 2011/05/06 06:00
CRDT- 2011/02/09 06:00
PHST- 2011/02/01 00:00 [received]
PHST- 2011/02/02 00:00 [accepted]
PHST- 2011/02/09 06:00 [entrez]
PHST- 2011/02/09 06:00 [pubmed]
PHST- 2011/05/06 06:00 [medline]
AID - S0006-291X(11)00193-8 [pii]
AID - 10.1016/j.bbrc.2011.02.010 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2011 Mar 11;406(2):194-9. doi: 
      10.1016/j.bbrc.2011.02.010. Epub 2011 Feb 15.