Expression of NSAID-activated gene-1 by EGCG in head and neck cancer: involvement of ATM-dependent p53 expression.

Abstract

Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, possesses remarkable chemopreventive and therapeutic potential against various types of cancer, including head and neck squamous cell carcinoma (HNSCC). However, the molecular mechanism involved is not completely understood. Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), a transforming growth factor β superfamily protein, is shown to be induced by several antitumorigenic compounds and to exhibit proapoptotic and antitumorigenic activities. In this report, we demonstrate that EGCG transcriptionally induced the expression of NAG-1 during EGCG-induced apoptosis of HNSCC cells. Reporter assays, using the luciferase constructs containing the NAG-1 promoter, demonstrate that p53 is required for EGCG-mediated activation of NAG-1. Overexpression of NAG-1 enhanced the apoptotic effect of EGCG, whereas suppression of NAG-1 expression by small interfering RNA attenuated EGCG-induced apoptosis in HNSCC cells. Subsequently, we found that ataxia-telangiectasia mutated (ATM) plays an important role in activating these proapoptotic proteins (NAG-1 and p53) and cell cycle inhibitor (p21). Furthermore, EGCG significantly inhibited tumor formation as assessed by xenograft models, and this result is accompanied with induction of apoptotic cells and NAG-1 expression in tumor tissue samples. Taken together, these results demonstrate for the first time that EGCG induces apoptosis via ATM/p53-dependent NAG-1 expression in HNSCC, providing an additional mechanistic explanation for the apoptotic activity of EGCG.

• Authors: Sung Un Kang, Bok-Soon Lee, Seong-Ho Lee, Seung Joon Baek, Yoo Seob Shin, Chul-Ho Kim
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 24 Issue 6 Pg. 986-99 (Jun 2013) ISSN: 1873-4847 [Electronic] United States
• PMID: 23017582 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Anticarcinogenic Agents
• GDF15 protein, human
• Growth Differentiation Factor 15
• RNA, Small Interfering
• Tumor Suppressor Protein p53
• Catechin
• epigallocatechin gallate
• ATM protein, human
• Ataxia Telangiectasia Mutated Proteins

Topics

• Anticarcinogenic Agents (pharmacology)
• Apoptosis
• Ataxia Telangiectasia Mutated Proteins (genetics, metabolism)
• Carcinoma, Squamous Cell (drug therapy, genetics, metabolism)
• Catechin (analogs & derivatives, pharmacology)
• Cell Line, Tumor
• Growth Differentiation Factor 15 (genetics)
• Head and Neck Neoplasms (drug therapy, genetics, metabolism)
• Heterografts
• Humans
• RNA, Small Interfering (metabolism)
• Squamous Cell Carcinoma of Head and Neck
• Tumor Suppressor Protein p53 (genetics, metabolism)