KMID : 1161420110140040325
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Journal of Medicinal Food 2011 Volume.14 No. 4 p.325 ~ p.333
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Citrus Flavonoids Luteolin, Apigenin, and Quercetin Inhibit Glycogen Synthase Kinase-3¥â Enzymatic Activity by Lowering the Interaction Energy Within the Binding Cavity
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Johnson Jodee L.
Rupasinghe Sanjeewa G. Stefani Felicia Schuler Mary A. de Mejia Elvira Gonzalez
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Abstract
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Pancreatic cancer studies have shown that inhibition of glycogen synthase kinase-3¥â (GSK-3¥â) leads to decreased cancer cell proliferation and survival by abrogating nuclear factor ¥êB (NF¥êB) activity. In this investigation, various citrus compounds, including flavonoids, phenolic acids, and limonoids, were individually investigated for their inhibitory effects on GSK-3¥â by using a luminescence assay. Of the 22 citrus compounds tested, the flavonoids luteolin, apigenin, and quercetin had the highest inhibitory effects on GSK-3¥â, with 50% inhibitory values of 1.5, 1.9, and 2.0?¥ìM, respectively. Molecular dockings were then performed to determine the potential interactions of each citrus flavonoid with GSK-3¥â. Luteolin, apigenin, and quercetin were predicted to fit within the binding pocket of GSK-3¥â with low interaction energies (?76.4, ?76.1, and ?84.6?kcal¡¤mol?1, respectively) and low complex energies (?718.1, ?688.1, and ?719.7?kcal¡¤mol?1, respectively). Our results indicate that several citrus flavonoids inhibit GSK-3¥â activity and suggest that these have potential to suppress the growth of pancreatic tumors.
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KEYWORD
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Glycogen synthase kinase-3¥â, GSK-3¥â, citrus compounds, flavonoids, luminescence assay, molecular docking
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