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Inhibition of glycogen synthase kinase‐3β and pancreatic cancer cell proliferation in vitro by citrus flavonoids
Author(s) -
Johnson Jodee,
Mejia Elvira Gonzalez
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.979.17
Subject(s) - hesperidin , chemistry , luteolin , nobiletin , naringin , apigenin , hesperetin , naringenin , quercetin , biochemistry , kaempferol , rutin , flavonoid , antioxidant , medicine , alternative medicine , pathology , chromatography
Glycogen synthase kinase‐3β (GSK‐3β) inhibition contributes to decreased pancreatic cancer cell proliferation and survival. The objective was to investigate the inhibitory effects of citrus compounds on GSK‐3β activity. We also evaluated the effects of these compounds on pancreatic cancer cells (Panc‐1 and BxPC‐3) in vitro . Flavonoids (luteolin, apigenin, quercetin, kaempferol, flavone, hesperetin, naringenin, nobiletin, tangeretin, rutin, hesperidin, narirutin, eriocitrin, naringin and neohesperidin), phenolic acids (caffeic and chlorogenic acid), limonoids (nomilin, obacunone, limonin and azadirachtin), and ascorbic acid were investigated for their inhibitory effects. Luteolin, apigenin and quercetin had the highest inhibitory effects on GSK‐3β activity with IC 50 values of 1.5, 1.9 and 2.0 μM, respectively. Molecular docking demonstrated that these compounds also had the lowest interaction energies (−76.4, −76.1 and −84.6 kcal·mol −1 , respectively). A correlation (r 2 = 0.71) was found between inhibition of GSK‐3β activity and interaction energies for the most active compounds. Apigenin caused great inhibition to Panc‐1 and BxPC‐3 cells (IC 50 = 41 μM and 12 μM, respectively). In conclusion, our results indicate that several citrus flavonoids inhibit GSK‐3β activity directly by binding in the active site of the enzyme, and suggest their potential to suppress pancreatic cancer tumor growth. Grant Funding Source : USDA