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EGCG inhibits activation of HER3 and expression of cyclooxygenase-2 in human colon cancer cells.
J Exp Ther Oncol. 2005; 5(1):69-78.JE

Abstract

Increased expression of COX-2 appears to play an important role in the development of colorectal cancer. The level of COX-2 expression is regulated by various factors including activation of members of the EGFR family of RTKs. We previously reported that in HT29 human colon cancer cells EGCG, the major biologically active component of green tea, inhibits activation of two members of this family, EGFR and HER2, and multiple downstream signaling pathways. In this study we examined the effects of EGCG on the HER3 RTK and on COX-2 expression in the SW837 human colon cancer cell line that expresses a high level and constitutive activation of HER3 and also expresses a high level of COX-2. Treatment of these cells with 20 microg/ml of EGCG (the IC50 concentration for growth inhibition) caused, within 6 hours, a decrease in the phosphorylated (i.e. activated) forms of not only EGFR and HER2, but also HER3. At 6 to 12 hours there was a decrease in the phosphorylated forms of the downstream signaling proteins ERK and Akt. Within 6 to 12 hours there was a decrease in cellular levels of both COX-2 protein and mRNA, and within 48 hours the cells displayed apoptosis. Reporter assays indicated that EGCG inhibited the transcriptional activities of the COX-2, AP-1, and NF-kappaB promoters. EGCG also caused a decrease in production of PGE2, a major product of COX-2. With a longer incubation time, 96 hours, a very low dose (1.0 microg/ml) of EGCG also caused inhibition of cell growth, inhibition of activation of EGFR, HER2, and HER3, a decrease in the levels of COX-2 and Bcl-xL proteins, and apoptosis. These results provide the first evidence that a low concentration of EGCG can inhibit activation of, at least, three members of the EGFR family of RTKs, and also inhibit COX-2 expression in colon cancer cells. These findings extend our previous evidence that EGCG may be useful in the chemoprevention and/or treatment of colorectal cancer.

Authors+Show Affiliations

Herbert Irving Comprehensive Cancer Center and Department of Medicine, Columbia University Medical Center, 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

16416603

Citation

Shimizu, Masahito, et al. "EGCG Inhibits Activation of HER3 and Expression of Cyclooxygenase-2 in Human Colon Cancer Cells." Journal of Experimental Therapeutics & Oncology, vol. 5, no. 1, 2005, pp. 69-78.
Shimizu M, Deguchi A, Joe AK, et al. EGCG inhibits activation of HER3 and expression of cyclooxygenase-2 in human colon cancer cells. J Exp Ther Oncol. 2005;5(1):69-78.
Shimizu, M., Deguchi, A., Joe, A. K., Mckoy, J. F., Moriwaki, H., & Weinstein, I. B. (2005). EGCG inhibits activation of HER3 and expression of cyclooxygenase-2 in human colon cancer cells. Journal of Experimental Therapeutics & Oncology, 5(1), 69-78.
Shimizu M, et al. EGCG Inhibits Activation of HER3 and Expression of Cyclooxygenase-2 in Human Colon Cancer Cells. J Exp Ther Oncol. 2005;5(1):69-78. PubMed PMID: 16416603.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - EGCG inhibits activation of HER3 and expression of cyclooxygenase-2 in human colon cancer cells. AU - Shimizu,Masahito, AU - Deguchi,Atsuko, AU - Joe,Andrew K, AU - Mckoy,Judith F, AU - Moriwaki,Hisataka, AU - Weinstein,I Bernard, PY - 2006/1/19/pubmed PY - 2006/3/11/medline PY - 2006/1/19/entrez SP - 69 EP - 78 JF - Journal of experimental therapeutics & oncology JO - J Exp Ther Oncol VL - 5 IS - 1 N2 - Increased expression of COX-2 appears to play an important role in the development of colorectal cancer. The level of COX-2 expression is regulated by various factors including activation of members of the EGFR family of RTKs. We previously reported that in HT29 human colon cancer cells EGCG, the major biologically active component of green tea, inhibits activation of two members of this family, EGFR and HER2, and multiple downstream signaling pathways. In this study we examined the effects of EGCG on the HER3 RTK and on COX-2 expression in the SW837 human colon cancer cell line that expresses a high level and constitutive activation of HER3 and also expresses a high level of COX-2. Treatment of these cells with 20 microg/ml of EGCG (the IC50 concentration for growth inhibition) caused, within 6 hours, a decrease in the phosphorylated (i.e. activated) forms of not only EGFR and HER2, but also HER3. At 6 to 12 hours there was a decrease in the phosphorylated forms of the downstream signaling proteins ERK and Akt. Within 6 to 12 hours there was a decrease in cellular levels of both COX-2 protein and mRNA, and within 48 hours the cells displayed apoptosis. Reporter assays indicated that EGCG inhibited the transcriptional activities of the COX-2, AP-1, and NF-kappaB promoters. EGCG also caused a decrease in production of PGE2, a major product of COX-2. With a longer incubation time, 96 hours, a very low dose (1.0 microg/ml) of EGCG also caused inhibition of cell growth, inhibition of activation of EGFR, HER2, and HER3, a decrease in the levels of COX-2 and Bcl-xL proteins, and apoptosis. These results provide the first evidence that a low concentration of EGCG can inhibit activation of, at least, three members of the EGFR family of RTKs, and also inhibit COX-2 expression in colon cancer cells. These findings extend our previous evidence that EGCG may be useful in the chemoprevention and/or treatment of colorectal cancer. SN - 1359-4117 UR - https://www.unboundmedicine.com/medline/citation/16416603/EGCG_inhibits_activation_of_HER3_and_expression_of_cyclooxygenase_2_in_human_colon_cancer_cells_ L2 - https://antibodies.cancer.gov/detail/CPTC-MAPK1-4 DB - PRIME DP - Unbound Medicine ER -