PMID- 12440226
OWN - NLM
STAT- MEDLINE
DCOM- 20030429
LR  - 20220310
IS  - 1359-4117 (Print)
IS  - 1359-4117 (Linking)
VI  - 2
IP  - 6
DP  - 2002 Nov-Dec
TI  - Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast 
      carcinoma cells by inhibiting EGFR-related pathways of signal transduction.
PG  - 350-9
AB  - In a recent study on head and neck squamous cell carcinoma (HNSCC) cells we found 
      that epigallocatechin-3-gallate (EGCG), a major biologically active component of 
      green tea, inhibited activation of the epidermal growth factor receptor (EGFR) 
      and related signaling pathways. Since activation of EGFR signaling pathways is 
      associated with angiogenesis, we examined the effects of EGCG on vascular 
      endothelial growth factor (VEGF) production by YCU-H891 HNSCC and MDA-MB-231 
      breast carcinoma cell lines, because we found that both of these cell lines 
      display autocrine activation of transforming growth factor-alpha (TGF-alpha)/EGFR 
      signaling and produce high levels of VEGF. Treatment with EGCG inhibited the 
      constitutive activation of the EGFR, Stat3, and Akt in both cell lines. These 
      changes were associated with inhibition of VEGF promoter activity and cellular 
      production of VEGF. Mechanistic studies indicated that inhibition of Stat3, but 
      not mitogen-activated protein kinase kinase (MEK)1 or phosphatidylinositol 
      3'-kinase (PI3K), significantly decreased VEGF promoter activity. However, the 
      inhibitory effects of a dominant negative Stat3 on VEGF expression was not as 
      strong as that produced by EGCG. An analysis of alternative pathways indicated 
      that EGCG strongly inhibited the constitutive activation of NF-kappa B in both 
      cell lines, and an NF-kappa B inhibitor strongly inhibited VEGF production. These 
      results suggest that EGCG inhibits VEGF production by inhibiting both the 
      constitutive activation of Stat3 and NF-kappa B, but not 
      extracellular-signal-regulated kinase (ERK) or Akt, in these cells. Therefore, 
      EGCG may be useful in treating HNSCC and breast carcinoma because it can exert 
      both antiproliferative and antiangiogenic activities.
FAU - Masuda, Muneyuki
AU  - Masuda M
AD  - Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, 
      Columbia University, HHSC-1509, 701 W. 168th Street, New York, NY 10032, USA.
FAU - Suzui, Masumi
AU  - Suzui M
FAU - Lim, Jin T E
AU  - Lim JT
FAU - Deguchi, Atsuko
AU  - Deguchi A
FAU - Soh, Jae-Won
AU  - Soh JW
FAU - Weinstein, I Bernard
AU  - Weinstein IB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Exp Ther Oncol
JT  - Journal of experimental therapeutics & oncology
JID - 9604933
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Chromones)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Lymphokines)
RN  - 0 (Morpholines)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 8R1V1STN48 (Catechin)
RN  - BQM438CTEL (epigallocatechin gallate)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (MAP3K1 protein, human)
RN  - EC 3.4.21.73 (Urokinase-Type Plasminogen Activator)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Breast Neoplasms/*metabolism
MH  - Carcinoma, Squamous Cell/*metabolism
MH  - Catechin/*analogs & derivatives/*pharmacology
MH  - Chromones/pharmacology
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Endothelial Growth Factors/*biosynthesis/genetics
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - ErbB Receptors/*antagonists & inhibitors
MH  - Flavonoids/pharmacology
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Head and Neck Neoplasms/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*biosynthesis/genetics
MH  - Luciferases/metabolism
MH  - Lymphokines/*biosynthesis/genetics
MH  - *MAP Kinase Kinase Kinase 1
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Models, Biological
MH  - Morpholines/pharmacology
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors
MH  - STAT3 Transcription Factor
MH  - Signal Transduction/*drug effects
MH  - Trans-Activators/genetics/metabolism
MH  - Transfection
MH  - Transforming Growth Factor alpha/metabolism
MH  - Tumor Cells, Cultured
MH  - Urokinase-Type Plasminogen Activator/antagonists & inhibitors
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 2002/11/21 04:00
MHDA- 2003/04/30 05:00
CRDT- 2002/11/21 04:00
PHST- 2002/11/21 04:00 [pubmed]
PHST- 2003/04/30 05:00 [medline]
PHST- 2002/11/21 04:00 [entrez]
AID - 10.1046/j.1359-4117.2002.01062.x [doi]
PST - ppublish
SO  - J Exp Ther Oncol. 2002 Nov-Dec;2(6):350-9. doi: 10.1046/j.1359-4117.2002.01062.x.