Abstract
Problem: The anti-tumor effects of the green tea compound epigallocatechin-3-gallate (EGCG) have not been previously studied in detail in head and neck squamous cell carcinoma (HNSCC) cells.
Methods: We examined the molecular effects of EGCG on human HNSCC cell line YCU-H891, focusing on the EGFR signaling pathway, since this cell line displayed autocrine activation of EGFR signaling pathways.
Results: The 70% lethal dose (IC70) of EGCG 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 which may account for the arrest in G1. EGCG also caused a decrease in the Bc1-2 and Bc1-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, Stat3, ERK, and Akt proteins and also inhibited NF-kB activity, c-fos, cyclin D1, and VEGF promoter activity and VEGF production. EGCG at 0.1 μg/mL (a concentration found in serum after oral administration) markedly enhanced the growth inhibitory effects of 5-FU and Taxol.
Conclusion: Taken together, these findings provide insights into molecular targets of EGCG, by which EGCG causes growth inhibition on HNSCC cells.
Significance: EGCG may be useful, when used alone or in combination with other agents, in the chemoprevention and/or treatment of HNSCC.
Support: None reported.