Piceatannol (Synonyms: Astringenin, transPicetannol, trans3,3',4,5'Tetrahydroxystilbene)

Piceatannol (3,3′,4,5′-trans-trihydroxystilbene) is a naturally occurring hydroxylated analogue of resveratrol ^[1]. Piceatannol inhibited mushroom tyrosinase with IC50 value of 1.53 mM ^[2]. piceatannol is a spleen tyrosine kinase (Syk) inhibitor, it is often used in studies involving Syk kinase-dependent cells [3,4], especially neutrophils [5,6], macrophages [7,8] and smooth muscle cells [9,10].

Piceatannol was used to specifically inhibit Syk, which is an important adaptor of FcγR cross-linking-induced downstream signaling. Application of Piceatannol aborted cyclin D1 expression induced by FcγR cross-linking in murine bone marrow-derived macrophages (BMM) [7]. Pre-incubation of piceatannol (100 nM for 1 h) increased neutrophil adhesion in the presence of E3MPO, reversing the non-adherent phenotype of the cells [5]. piceatannol inhibited Ang II-enhanced rat aortic smooth muscle cells (RASMCs) migration, and inhibited Ang II-stimulated phosphorylation of ERK1/2, p38 MAPK and Hsp27, pretreatment with piceatannol attenuated Ang II-increased sprout outgrowth from aortic rings [9].

Piceatannol (10 or 20 mg/kg/d, 3 weeks, oral) administration significantly decreases solid tumor growth in BALB/c mice injected with 4T1 mammary cancer cells [11]. Piceatannol (20 mg/kg/d, 9 days, oral) inhibits lung metastasis of MAT-Ly-Lu (MLL) cells in nude mice [12].

References:
[1]. Piotrowska H, Kucinska M, Murias M. Biological activity of piceatannol: leaving the shadow of resveratrol[J]. Mutation Research/Reviews in Mutation Research, 2012, 750(1): 60-82.
[2]. Yokozawa T, Kim Y J. Piceatannol inhibits melanogenesis by its antioxidative actions[J]. Biological and Pharmaceutical Bulletin, 2007, 30(11).
[3]. Pavanetto M, Zarpellon A, Borgo C, et al. Regulation of serotonin transport in human platelets by tyrosine kinase Syk[J]. Cellular Physiology and Biochemistry, 2011, 27(2): 139-148.
[4]. Beckmann S, Buro C, Dissous C, et al. The Syk kinase SmTK4 of Schistosoma mansoni is involved in the regulation of spermatogenesis and oogenesis[J]. PLoS Pathogens, 2010, 6(2): e1000769.
[5]. Hayes M J, Cambridge G. An IgM class anti-neutrophil cytoplasm antibody inhibits neutrophil adhesion and apoptosis via a Syk dependent signaling cascade[J]. Molecular immunology, 2004, 41(4): 457-468.
[6]. Ortiz‐Stern A, Rosales C. FcγRIIIB stimulation promotes β1 integrin activation in human neutrophils[J]. Journal of leukocyte biology, 2005, 77(5): 787-799.
[7]. Luo Y, Pollard J W, Casadevall A. Fcγ receptor cross-linking stimulates cell proliferation of macrophages via the ERK pathway[J]. Journal of Biological Chemistry, 2010, 285(6): 4232-4242.
[8]. Gevrey J C, Isaac B M, Cox D. Syk is required for monocyte/macrophage chemotaxis to CX3CL1 (Fractalkine)[J]. The Journal of Immunology, 2005, 175(6): 3737-3745.
[9]. Lau H K F, Ho J. Regulation of plasminogen activator inhibitor‿ secretion by urokinase and tissue plasminogen activator in rat epithelioid‐type smooth muscle cells[J]. British journal of haematology, 2002, 117(1): 151-158.
[10]. Lee H M, Lee C K, Lee S H, et al. p38 mitogen-activated protein kinase contributes to angiotensin II-stimulated migration of rat aortic smooth muscle cells[J]. Journal of pharmacological sciences, 2007, 105(1): 74-81.
[11]. Song H, Jung J I, Cho H J, et al. Inhibition of tumor progression by oral piceatannol in mouse 4T1 mammary cancer is associated with decreased angiogenesis and macrophage infiltration[J]. The Journal of nutritional biochemistry, 2015, 26(11): 1368-1378.
[12]. Kwon G T, Jung J I, Song H R, et al. Piceatannol inhibits migration and invasion of prostate cancer cells: possible mediation by decreased interleukin-6 signaling[J]. The Journal of nutritional biochemistry, 2012, 23(3): 228-238.