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Epigenetics of Tea Polyphenols in Cancer Prevention

茶多酚在癌症预防中的表观遗传学

基本信息

批准号：
7599223
负责人：
TRYGVE O TOLLEFSBOL
金额：
$ 24.07万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7599223
关键词：
Acetylation Affect Apoptosis Attention Azacitidine Beverages Binding Biological Models Breast Breast Cancer Cell Breast Cancer Prevention Cancer Control Cancer Etiology Cancer Patient Cells Cessation of life Chemopreventive Agent Chromosomes DNA Methylation DNA Methyltransferase DNA Modification Methylases Dietary Component Dietary Factors Down-Regulation E2F1 gene Enzymes Epigallocatechin Gallate Epigenetic Process Female Gene Expression Gene Expression Regulation Goals Green tea Histone Acetylation Histone Deacetylase Inhibitor Histone Deacetylation Histones In Vitro Incidence Investigation Laboratories Lead Malignant Neoplasms Measures Mediating Methylation Modeling Oral Oral Administration Outcome Study Pathway interactions Play Prevention therapy Process Property RNA Interference Regulation Regulator Genes Reporting Role TERT gene Tea Techniques Telomerase Telomerase inhibition Toxic effect Transcriptional Regulation Trichostatin A United States Work breast tumorigenesis cancer cell cancer prevention chemotherapy cytotoxic gallocatechol histone methyltransferase in vivo malignant breast neoplasm novel strategies polyphenol pre-clinical prevent promoter public health relevance response transcription factor tumor tumor progression tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Green tea is widely consumed as a popular beverage worldwide and has chemopreventive and anticancer properties. A major constituent of green tea is the polyphenol, (-)-epigallocatechin-3-gallate (EGCG), that is effective in the prevention of breast cancer, a leading cause of cancer-related deaths among females in the United States. Many studies have indicated that EGCG inhibits DNA methyltransferase 1 and telomerase activity which play critical roles in the progression of tumorigenesis. Telomerase inhibition by EGCG leads to apoptosis of cancer cells and oral administration of EGCG is effective especially in telomerase-expressing cancer cells. We discovered that EGCG down-regulates telomerase primarily through transcriptional control of the telomerase regulatory gene, hTERT, and other laboratories have now reported similar findings. Alterations of the hTERT gene by green tea polyphenols involve changes in histone acetylation, DNA methylation, and transcription factor binding although the roles of other epigenetic processes and the in vivo mechanisms are not fully understood. The main hypothesis is that green tea polyphenols prevent the epigenetic processes that lead to telomerase activation in breast cancer. A secondary hypothesis is that green tea modulates the availability of the histone deacetylases (HDACs), histone methyltransferases (HMTases) and/or DNA methyltransferases (DNMTs) as well as key transcription factors to the hTERT promoter leading to breast cancer prevention. Aim 1 will assess the role of green tea polyphenols in controlling histone methylation and acetylation at key residues known to be involved in hTERT regulation. Aim 2 will evaluate the interactions of the hTERT promoter with key epigenetic modulators such as the HDACs, HMTases and DNMTs as well as major transcriptional regulators of hTERT. Aim 3 is to measure the in vivo effects of green tea polyphenols on epigenetic processes controlling the hTERT promoter using breast preclinical cancer prevention models. Since green tea has promise in reducing the incidence of breast cancer, the goal of this proposal is to determine the epigenetic mechanisms, both in vitro and in vivo, whereby this common dietary component decreases the incidence of breast cancer. It is intended that the outcome of these studies will facilitate more effective uses of green tea and/or polyphenols in cancer prevention and will help elucidate the mechanisms through which green tea imparts its chemopreventive properties. PUBLIC HEALTH RELEVANCE : Chemotherapy of cancer patients often produces unsatisfactory and/or toxic effects. Investigations into non-toxic or less cytotoxic modes of cancer prevention or treatment are therefore warranted. The proposed studies will help elucidate how dietary green tea imparts its chemopreventive and anticancer effects and may lead to novel approaches to cancer prevention through control not only of dietary factors, but also through epigenetic processes.

描述（由申请人提供）：