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(-)-Epigallocatechin gallate inhibits growth and activation of the VEGF/VEGFR axis in human colorectal cancer cells.
Chem Biol Interact. 2010 May 14; 185(3):247-52.CB

Abstract

(-)-Epigallocatechin gallate (EGCG), the major constituent of green tea, inhibits the growth of colorectal cancer cells by inhibiting the activation of various types of receptor tyrosine kinases (RTKs). The RTK vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) axis induces tumor angiogenesis in colorectal cancer. This study examined the effects of EGCG on the activity of the VEGF/VEGFR axis and the expression of hypoxia-inducible factor (HIF)-1alpha, which promotes angiogenesis by elevating VEGF levels, in human colorectal cancer cells. Total and phosphorylated (i.e., activated) form (p-VEGFR-2) of VEGFR-2 proteins were overexpressed in a series of human colorectal cancer cell lines. Within 3h, EGCG caused a decrease in the expression of HIF-1alpha protein and VEGF, HIF-1alpha, insulin-like growth factor (IGF)-1, IGF-2, epidermal growth factor (EGF), and heregulin mRNAs in SW837 colorectal cancer cells, which express a constitutively activated VEGF/VEGFR axis. A decrease was also observed in the expression of VEGFR-2, p-VEGFR-2, p-IGF-1 receptor, p-ERK, and p-Akt proteins within 6h after EGCG treatment. Drinking EGCG significantly inhibited the growth of SW837 xenografts in nude mice, and this was associated with the inhibition of the expression and activation of VEGFR-2. The consumption of EGCG also inhibited activation of ERK and Akt, both of which are downstream signaling molecules of the VEGF/VEGFR axis, and reduced the expression of VEGF mRNA in xenografts. These findings suggest that EGCG may exert, at least in part, growth-inhibitory effects on colorectal cancer cells by inhibiting the activation of the VEGF/VEGFR axis through suppressing the expression of HIF-1alpha and several major growth factors. EGCG may therefore be useful in the chemoprevention and/or treatment of colorectal cancer.

Authors+Show Affiliations

Department of Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. shimim-gif@umin.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

20346928

Citation

Shimizu, Masahito, et al. "(-)-Epigallocatechin Gallate Inhibits Growth and Activation of the VEGF/VEGFR Axis in Human Colorectal Cancer Cells." Chemico-biological Interactions, vol. 185, no. 3, 2010, pp. 247-52.
Shimizu M, Shirakami Y, Sakai H, et al. (-)-Epigallocatechin gallate inhibits growth and activation of the VEGF/VEGFR axis in human colorectal cancer cells. Chem Biol Interact. 2010;185(3):247-52.
Shimizu, M., Shirakami, Y., Sakai, H., Yasuda, Y., Kubota, M., Adachi, S., Tsurumi, H., Hara, Y., & Moriwaki, H. (2010). (-)-Epigallocatechin gallate inhibits growth and activation of the VEGF/VEGFR axis in human colorectal cancer cells. Chemico-biological Interactions, 185(3), 247-52. https://doi.org/10.1016/j.cbi.2010.03.036
Shimizu M, et al. (-)-Epigallocatechin Gallate Inhibits Growth and Activation of the VEGF/VEGFR Axis in Human Colorectal Cancer Cells. Chem Biol Interact. 2010 May 14;185(3):247-52. PubMed PMID: 20346928.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - (-)-Epigallocatechin gallate inhibits growth and activation of the VEGF/VEGFR axis in human colorectal cancer cells. AU - Shimizu,Masahito, AU - Shirakami,Yohei, AU - Sakai,Hiroyasu, AU - Yasuda,Yoichi, AU - Kubota,Masaya, AU - Adachi,Seiji, AU - Tsurumi,Hisashi, AU - Hara,Yukihiko, AU - Moriwaki,Hisataka, Y1 - 2010/03/25/ PY - 2010/01/12/received PY - 2010/03/17/revised PY - 2010/03/18/accepted PY - 2010/3/30/entrez PY - 2010/3/30/pubmed PY - 2010/5/11/medline SP - 247 EP - 52 JF - Chemico-biological interactions JO - Chem Biol Interact VL - 185 IS - 3 N2 - (-)-Epigallocatechin gallate (EGCG), the major constituent of green tea, inhibits the growth of colorectal cancer cells by inhibiting the activation of various types of receptor tyrosine kinases (RTKs). The RTK vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) axis induces tumor angiogenesis in colorectal cancer. This study examined the effects of EGCG on the activity of the VEGF/VEGFR axis and the expression of hypoxia-inducible factor (HIF)-1alpha, which promotes angiogenesis by elevating VEGF levels, in human colorectal cancer cells. Total and phosphorylated (i.e., activated) form (p-VEGFR-2) of VEGFR-2 proteins were overexpressed in a series of human colorectal cancer cell lines. Within 3h, EGCG caused a decrease in the expression of HIF-1alpha protein and VEGF, HIF-1alpha, insulin-like growth factor (IGF)-1, IGF-2, epidermal growth factor (EGF), and heregulin mRNAs in SW837 colorectal cancer cells, which express a constitutively activated VEGF/VEGFR axis. A decrease was also observed in the expression of VEGFR-2, p-VEGFR-2, p-IGF-1 receptor, p-ERK, and p-Akt proteins within 6h after EGCG treatment. Drinking EGCG significantly inhibited the growth of SW837 xenografts in nude mice, and this was associated with the inhibition of the expression and activation of VEGFR-2. The consumption of EGCG also inhibited activation of ERK and Akt, both of which are downstream signaling molecules of the VEGF/VEGFR axis, and reduced the expression of VEGF mRNA in xenografts. These findings suggest that EGCG may exert, at least in part, growth-inhibitory effects on colorectal cancer cells by inhibiting the activation of the VEGF/VEGFR axis through suppressing the expression of HIF-1alpha and several major growth factors. EGCG may therefore be useful in the chemoprevention and/or treatment of colorectal cancer. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/20346928/____Epigallocatechin_gallate_inhibits_growth_and_activation_of_the_VEGF/VEGFR_axis_in_human_colorectal_cancer_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(10)00199-7 DB - PRIME DP - Unbound Medicine ER -