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

  • J Agric Food Chem. 2019 Feb 13;67(6):1656-1665. doi: 10.1021/acs.jafc.8b05447.
Long Ma  1 ,  Xiuqi Cao  1 ,  Haiyue Wang  1 ,  Kui Lu  1 ,  Ying Wang  1 ,  Chunhao Tu  1 ,  Yujie Dai  1 ,  Yuanyuan Meng  1 ,  Yuyin Li  1 ,  Peng Yu  1 ,  Shuli Man  1 ,  Aipo Diao  1
Affiliations
  • 1. 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.
PMID: 30694659 DOI: 10.1021/acs.jafc.8b05447
Abstract

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.

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