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Targeting Epigenetic ‘Readers’ with Natural Compounds for Cancer Interception

Journal of Cancer Prevention 2020년 25권 4호 p.189 ~ 203
Damiani Elisabetta, Duran Munevver N., Mohan Nivedhitha, Rajendran Praveen, Dashwood Roderick H.,
소속 상세정보
 ( Damiani Elisabetta ) - Polytechnic University of Marche Department of Life and Environmental Sciences
 ( Duran Munevver N. ) - Texas A&M Health Science Center Center for Epigenetics and Disease Prevention
 ( Mohan Nivedhitha ) - Texas A&M Health Science Center Center for Epigenetics and Disease Prevention
 ( Rajendran Praveen ) - Texas A&M Health Science Center Center for Epigenetics and Disease Prevention
 ( Dashwood Roderick H. ) - Texas A&M Health Science Center Center for Epigenetics and Disease Prevention

Abstract


Natural compounds from diverse sources, including botanicals and commonly consumed foods and beverages, exert beneficial health effects via mechanisms that impact the epigenome and gene expression during disease pathogenesis. By targeting the so-called epigenetic ‘readers’, ‘writers’, and ‘erasers’, dietary phytochemicals can reverse abnormal epigenome signatures in cancer cells and preneoplastic stages. Thus, such agents provide avenues for cancer interception via prevention or treatment/therapeutic strategies. To date, much of the focus on dietary agents has been directed towards writers (e.g., histone acetyltransferases) and erasers (e.g., histone deacetylases), with less attention given to epigenetic readers (e.g., BRD proteins). The drug JQ1 was developed as a prototype epigenetic reader inhibitor, selectively targeting members of the bromodomain and extraterminal domain (BET) family, such as BRD4. Clinical trials with JQ1 as a single agent, or in combination with standard of care therapy, revealed antitumor efficacy but not without toxicity or resistance. In pursuit of second-generation epigenetic reader inhibitors, attention has shifted to natural sources, including dietary agents that might be repurposed as ‘JQ1-like’ bioactives. This review summarizes the current status of nascent research activity focused on natural compounds as inhibitors of BET and other epigenetic ‘reader’ proteins, with a perspective on future directions and opportunities.

키워드

Bromodomains; Chromodomains; Cancer prevention; Epigenetics; Natural compounds

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