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J Agric Food Chem. 2019 Feb 13;67(6):1656-1665. doi: 10.1021/acs.jafc.8b05447. Epub 2019 Jan 29.

Discovery of Myricetin as a Potent Inhibitor of Human Flap Endonuclease 1, Which Potentially Can Be Used as Sensitizing Agent against HT-29 Human Colon Cancer Cells.

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State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology (MOE), Tianjin Key Laboratory of Industrial Microbiology, School of Biotechnology , Tianjin University of Science & Technology , Tianjin 300457 , China.


Human flap endonuclease 1 (hFEN1) is instrumental in DNA replication and repair. It is able to cleave the 5' single-stranded protrusion (also known as 5' flap) resulting from strand displacement reactions. In light of its crucial functions, hFEN1 is now deemed as a nontrivial target in the DNA damage response system for anticancer drug development. Herein, we report that myricetin and some natural flavonoids are able to inhibit hFEN1. Structure-activity relationship, inhibitory mechanisms, molecular docking, and cancer cell-based assays have been performed. Our original findings expand the activity of flavonoids and may pave the way for flavonoid-assisted targeted cancer therapy.


colon cancer treatment; flavonoids; human flap endonuclease 1 (hFEN1); inhibitor; molecular docking; myricetin; sensitizing effect; structure−activity relationship analysis

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