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Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction.
J Exp Ther Oncol. 2002 Nov-Dec; 2(6):350-9.JE

Abstract

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.

Authors+Show Affiliations

Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, HHSC-1509, 701 W. 168th Street, New York, NY 10032, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12440226

Citation

Masuda, Muneyuki, et al. "Epigallocatechin-3-gallate Decreases VEGF Production in Head and Neck and Breast Carcinoma Cells By Inhibiting EGFR-related Pathways of Signal Transduction." Journal of Experimental Therapeutics & Oncology, vol. 2, no. 6, 2002, pp. 350-9.
Masuda M, Suzui M, Lim JT, et al. Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction. J Exp Ther Oncol. 2002;2(6):350-9.
Masuda, M., Suzui, M., Lim, J. T., Deguchi, A., Soh, J. W., & Weinstein, I. B. (2002). Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction. Journal of Experimental Therapeutics & Oncology, 2(6), 350-9.
Masuda M, et al. Epigallocatechin-3-gallate Decreases VEGF Production in Head and Neck and Breast Carcinoma Cells By Inhibiting EGFR-related Pathways of Signal Transduction. J Exp Ther Oncol. 2002 Nov-Dec;2(6):350-9. PubMed PMID: 12440226.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction. AU - Masuda,Muneyuki, AU - Suzui,Masumi, AU - Lim,Jin T E, AU - Deguchi,Atsuko, AU - Soh,Jae-Won, AU - Weinstein,I Bernard, PY - 2002/11/21/pubmed PY - 2003/4/30/medline PY - 2002/11/21/entrez SP - 350 EP - 9 JF - Journal of experimental therapeutics & oncology JO - J Exp Ther Oncol VL - 2 IS - 6 N2 - 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. SN - 1359-4117 UR - https://www.unboundmedicine.com/medline/citation/12440226/Epigallocatechin_3_gallate_decreases_VEGF_production_in_head_and_neck_and_breast_carcinoma_cells_by_inhibiting_EGFR_related_pathways_of_signal_transduction_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1359-4117&date=2002&volume=2&issue=6&spage=350 DB - PRIME DP - Unbound Medicine ER -