CCR Focus Archive
Immunotherapy: Facts and Hopes
Effects of Epigallocatechin-3-gallate on Growth, Epidermal Growth Factor Receptor Signaling Pathways, Gene Expression, and Chemosensitivity in Human Head and Neck Squamous Cell Carcinoma Cell Lines
Muneyuki Masuda, Masumi Suzui and I. Bernard Weinstein
Muneyuki Masuda
Masumi Suzui
I. Bernard Weinstein
DOI: Published December 2001
The antitumor effects of the green tea compound epigallocatechin-3-gallate (EGCG) have not been studied in detail previously in head and neck squamous cell carcinoma (HNSCC) cells. Overexpression of the epidermal growth factor receptor (EGFR) occurs frequently in HNSCC, which is an adverse prognostic factor. Therefore, we examined in detail the molecular effects of EGCG on two human HNSCC cell lines, YCU-N861 and YCU-H891, focusing on the EGFR signaling pathway. The 70% lethal dose (IC70) of EGCG for both cell lines was 10 μg/ml. Treatment with EGCG increased the proportion of cells in the G1 phase of the cell cycle and induced apoptosis. In cells treated with EGCG, there was a decrease in the cyclin D1 protein, an increase in the p21Cip1 and p27Kip1 proteins, and a reduction in the hyperphosphorylated form of pRB, changes that may account for the arrest in G1. EGCG also caused a decrease in the Bcl-2 and Bcl-XL proteins, an increase in the Bax protein, and activation of caspase 9, suggesting that EGCG induces apoptosis via a mitochondrial pathway. Treatment with EGCG inhibited phosphorylation of the EGFR, signal transducer and activator of transcription3 (Stat3), and extracellular regulated kinase (ERK) proteins and also inhibited basal and transforming growth factor-α-stimulated c-fos and cyclin D1 promoter activity. EGCG at 0.1 μg/ml (a concentration found in serum after oral administration) markedly enhanced the growth-inhibitory effects of 5-fluorouracil. Taken together, these findings provide insights into molecular mechanisms of growth inhibition by EGCG and suggest that this naturally occurring compound may be useful, when used alone or in combination with other agents, in the chemoprevention and/or treatment of HNSCC.
Revision received September 10, 2001.
Thank you for sharing this Clinical Cancer Research article.
You are going to email the following Effects of Epigallocatechin-3-gallate on Growth, Epidermal Growth Factor Receptor Signaling Pathways, Gene Expression, and Chemosensitivity in Human Head and Neck Squamous Cell Carcinoma Cell Lines
Message Subject (Your Name) has forwarded a page to you from Clinical Cancer Research
Message Body (Your Name) thought you would be interested in this article in Clinical Cancer Research.
Clin Cancer Res December 1 2001 (7) (12) 4220-4229;
HER-2/neu Overexpression As a Poor Prognostic Factor for Patients with Metastatic Breast Cancer undergoing High-dose Chemotherapy with Autologous Stem Cell Transplantation
Synergistic Chemsensitization and Inhibition of Tumor Growth and Metastasis by the Antisense Oligodeoxynucleotide Targeting Clusterin Gene in a Human Bladder Cancer Model
Circulating Tumor Cell Clusters in the Peripheral Blood of Colorectal Cancer Patients
Experimental Therapeutics, Preclinical Pharmacology
Ring Finger Protein 43 as a New Target for Cancer Immunotherapy
Antifolate Resistance in a HeLa Cell Line Associated With Impaired Transport Independent of the Reduced Folate Carrier
ZD6474, a Potent Inhibitor of Vascular Endothelial Growth Factor Signaling, Combined With Radiotherapy
Show more Experimental Therapeutics, Preclinical Pharmacology
About Clinical Cancer Research