Targeting Epigenetic 'Readers' with Natural Compounds for Cancer Interception

Elisabetta Damian; Munevver N. Duran; Nivedhitha Mohan; Praveen Rajendran; Roderick H. Dashwood

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자료유형: 학술저널

저자정보: Elisabetta Damian (Polytechnic University of the Marche) Munevver N. Duran (Texas A&M Health Science Center) Nivedhitha Mohan (Texas A&M Health Science Center) Praveen Rajendran (Texas A&M Health Science Center) Roderick H. Dashwood (Texas A&M Health Science Center)

저널정보: 대한암예방학회 대한암예방학회지 대한암예방학회지 제25권 제4호

발행연도: 2020.1

수록면: 189 - 203 (15page)

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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 socalled 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. Key Words Bromodomains, Chromodomains, Cancer prevention, Epigenetics, Natural compounds

#Bromodomains #Chromodomains #Cancer prevention #Epigenetics #Natural compounds

참고문헌 (145)

참고문헌 신청

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