Piceatannol

SYK

244, 24

Female BALB/c mice with dextran sulfate sodium (DSS)-induced colitis

Dissolved in DMSO, final concentrations ca.50 uM

Dissolved in DMSO, and diluted in corn oil

Piceatannol displays ca.10-fold selectivity for Syk over Lyn. Piceatannol treatment in RBL-2H3 cells strongly inhibits the antigen-stimulated phosphorylation of Syk and of most other cellular proteins but not the receptor beta or gamma subunit, in a dose-dependent manner. Piceatannol is also a potent inhibitor of histamine release in mast cells. Selective inhibition of Syk by Piceatannol blocks receptor-mediated down-stream cellular responses in mast cells including prevention of 1, 4, 5-IP3 synthesis, secretion and membrane ruffling and spreading. [1] Piceatannol also potently inhibits PKA, PKC, MLCK, and CDPK with IC50 of 3 uM, 8 uM, 12 uM, and 19 uM, respectively. [2] Piceatannol selectively prevents the IFNalpha-induced tyrosine phosphorylation of STAT3 and -5 but not STAT1 and -2, paralleled by the loss of Jak1 and IFNAR1 tyrosine phosphorylation but not Tyk2 and IFNAR2. [3] Piceatannol potently induces apoptotic cell death in BJAB Burkitt-like lymphoma cells with ED50 of 25 uM, through the activation of caspase-3 and mitochondrial permeability transition independent of the CD95/Fas signaling pathway. [4] Piceatannol inhibits NF-kappaB activation induced by TNF, H2O2, PMA, LPS, okadaic acid, and ceramide. Piceatannol suppresses the expression of TNF-induced NF-kappaB-dependent reporter gene and of matrix metalloprotease-9, cyclooxygenase-2, and cyclin D1 independent of Syk kinase, by blocking TNF-induced IkappaBalpha phosphorylation, p65 phosphorylation, p65 nuclear translocation, and IkappaBalpha kinase activation. [5] Piceatannol directly binds with PI3K in an ATP-competitive manner, and suppresses PI3K activity with anti-atherosclerotic effects more effectively than resveratrol. [8] Piceatannol inhibits androgen-dependent (AD) and androgen-independent (AI) CaP cell proliferation, which is accompanied by reduced expression of mTOR and its key effectors AKT and eIF4EBP-1. [10]

72 hours and 1 week

Cells are exposed to increasing concentrations of Piceatannol. For the determination of cell proliferation, cells are assayed at 72 hours by trypan blue exclusion using a hemocytometer. After 1 week, colonies are stained with 1.25% crystal violet and quantified by measuring the absorbance at 595 nm.

Piceatannol, a natural stilbene, is a selective Syk inhibitor and ~10-fold selectivity versus Lyn.