Baicalein, 7,8-Dihydroxyflavone and Myricetin as Potent Inhibitors of Human Ornithine Decarboxylase

doi:10.3390/nu12123867

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24374

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24374

Title:	Baicalein, 7,8-Dihydroxyflavone and Myricetin as Potent Inhibitors of Human Ornithine Decarboxylase
Authors:	Liu, YC;Liu, YL;Hsieh, JY;Wang, CH;Lin, CL;Liu, GY;Hung, HC
Keywords:	ornithine decarboxylase;chemoprevention;molecular docking simulations;baicalein;7;8-dihydroxyflavone;myricetin
Date:	2020
Issue Date:	2022-08-09T08:01:15Z (UTC)
Publisher:	MDPI
Abstract:	Background: Human ornithine decarboxylase (ODC) is a well-known oncogene, and the discovery of ODC enzyme inhibitors is a beneficial strategy for cancer therapy and prevention. Methods: We examined the inhibitory effects of a variety of flavone and flavonol derivatives on ODC enzymatic activity, and performed in silico molecular docking of baicalein, 7,8-dihydroxyflavone and myricetin to the whole dimer of human ODC to investigate the possible binding site of these compounds on ODC. We also examined the cytotoxic effects of these compounds with cell-based studies. Results: Baicalein, 7,8-dihydroxyflavone and myricetin exhibited significant ODC suppression activity with IC50 values of 0.88 mu M, 2.54 mu M, and 7.3 mu M, respectively, which were much lower than that of the active-site irreversible inhibitor alpha-DL-difluoromethylornithine (IC50, the half maximal inhibitory concentration, of approximately 100 mu M). Kinetic studies and molecular docking simulations suggested that baicalein, and 7,8-dihydroxyflavone act as noncompetitive inhibitors that are hydrogen-bonded to the region near the active site pocket in the dimer interface of the enzyme. Baicalein and myricetin suppress cell growth and induce cellular apoptosis, and both of these compounds suppress the ODC-evoked anti-apoptosis of cells. Conclusions: Therefore, we suggest that the flavone or flavonol derivatives baicalein, 7,8-dihydroxyflavone, and myricetin are potent chemopreventive and chemotherapeutic agents that target ODC.
URI:	http://dx.doi.org/10.3390/nu12123867 https://www.webofscience.com/wos/woscc/full-record/WOS:000602483000001 https://ir.csmu.edu.tw:8080/handle/310902500/24374
Relation:	NUTRIENTS ,2020 ,v12 ,issue 12
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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