TY - JOUR
T1 - Citrus flavonoids luteolin, apigenin, and quercetin inhibit glycogen synthase kinase-3β enzymatic activity by lowering the interaction energy within the binding cavity
AU - Johnson, Jodee L.
AU - Rupasinghe, Sanjeewa G.
AU - Stefani, Felicia
AU - Schuler, Mary A.
AU - Gonzalez De Mejia, Elvira
PY - 2011/4/1
Y1 - 2011/4/1
N2 - Pancreatic cancer studies have shown that inhibition of glycogen synthase kinase-3β (GSK-3β) leads to decreased cancer cell proliferation and survival by abrogating nuclear factor κB (NFκB) activity. In this investigation, various citrus compounds, including flavonoids, phenolic acids, and limonoids, were individually investigated for their inhibitory effects on GSK-3β by using a luminescence assay. Of the 22 citrus compounds tested, the flavonoids luteolin, apigenin, and quercetin had the highest inhibitory effects on GSK-3β, with 50% inhibitory values of 1.5, 1.9, and 2.0μM, respectively. Molecular dockings were then performed to determine the potential interactions of each citrus flavonoid with GSK-3β. Luteolin, apigenin, and quercetin were predicted to fit within the binding pocket of GSK-3β with low interaction energies (-76.4, -76.1, and -84.6kcalmol-1, respectively) and low complex energies (-718.1, -688.1, and -719.7kcalmol -1, respectively). Our results indicate that several citrus flavonoids inhibit GSK-3β activity and suggest that these have potential to suppress the growth of pancreatic tumors.
AB - Pancreatic cancer studies have shown that inhibition of glycogen synthase kinase-3β (GSK-3β) leads to decreased cancer cell proliferation and survival by abrogating nuclear factor κB (NFκB) activity. In this investigation, various citrus compounds, including flavonoids, phenolic acids, and limonoids, were individually investigated for their inhibitory effects on GSK-3β by using a luminescence assay. Of the 22 citrus compounds tested, the flavonoids luteolin, apigenin, and quercetin had the highest inhibitory effects on GSK-3β, with 50% inhibitory values of 1.5, 1.9, and 2.0μM, respectively. Molecular dockings were then performed to determine the potential interactions of each citrus flavonoid with GSK-3β. Luteolin, apigenin, and quercetin were predicted to fit within the binding pocket of GSK-3β with low interaction energies (-76.4, -76.1, and -84.6kcalmol-1, respectively) and low complex energies (-718.1, -688.1, and -719.7kcalmol -1, respectively). Our results indicate that several citrus flavonoids inhibit GSK-3β activity and suggest that these have potential to suppress the growth of pancreatic tumors.
KW - GSK-3β
KW - Glycogen synthase kinase-3β
KW - citrus compounds
KW - flavonoids
KW - luminescence assay
KW - molecular docking
UR - http://www.scopus.com/inward/record.url?scp=79953173629&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953173629&partnerID=8YFLogxK
U2 - 10.1089/jmf.2010.0310
DO - 10.1089/jmf.2010.0310
M3 - Article
C2 - 21443429
AN - SCOPUS:79953173629
SN - 1096-620X
VL - 14
SP - 325
EP - 333
JO - Journal of medicinal food
JF - Journal of medicinal food
IS - 4
ER -