• Journal of Life Science
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• v.22 no.6
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• pp.815-822
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• 2012

Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene), a natural stilbene, is an analogue of resveratrol. Although recent experimental data have revealed the health benefit potency of piceatannol, the molecular mechanisms underlying the anti-cancer activity have not yet been studied in detail. In the present study, the further possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human lung cancer A549 cells were investigated. Exposure of A549 cells to piceatannol resulted in growth inhibition and induction of apoptosis. Apoptosis induction of A549 cells by piceatannol showed correlation with proteolytic activation of caspase-3, -8, and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase, phospholipase C-${\gamma}1$, ${\beta}$-catenin, and Inhibitor caspase-activated DNase. The increase in apoptosis by piceatannol treatment was also associated with an increase of pro-apoptotic Bax expression and decrease of anti-apoptotic Bcl-2 and Bcl-xL expression, and caused down-regulation of the inhibitor of apoptosis protein family members and up-regulation of Fas and Fas legend. In addition, piceatannol treatment markedly inhibited the expression of mRNA and proteins of inducible nitric oxide (NO) synthase, and the levels of NO production were progressively down-regulated by piceatannol treatment in a dose-dependent fashion. The results indicate that piceatannol may have therapeutic potential against human gastric cancer cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.9
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• pp.1226-1234
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• 2012

3,4,3',5'-Tetrahydroxy-trans-stilbene (piceatannol) is a derivative of resveratrol with a variety of biological activities, including anti-inflammatory, anti-proliferative, and anti-cancer activities. We assessed the mechanisms by which piceatannol inhibits inflammatory responses using lipopolysaccharide (LPS)-treated Raw264.7 murine macrophages. Piceatannol (0~10 ${\mu}mol/L$) decreased LPS-induced release of nitric oxide, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, and inhibited LPS-induced protein expression of inducible nitric oxide synthase (iNOS). Activation of nuclear factor-kappaB (NF-${\kappa}B$), activator protein (AP)-1, and signal transducer and activator of transcription 3 (STAT3) are crucial steps during an inflammatory response. Piceatannol prevented LPS-induced degradation of inhibitor of ${\kappa}B$ ($I{\kappa}B$), translocation of p65 to the nucleus, and phosphorylation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Additionally, piceatannol inhibited LPS-induced phosphorylation of STAT3 and IL-6-induced translocation of STAT3 to the nucleus. Furthermore, piceatannol increased the protein and mRNA levels of hemeoxygenase (HO)-1, the rate-limiting enzyme of heme catabolism that plays a critical role in mediating antioxidant and anti-inflammatory effects. Piceatannol further induced antioxidant response elements (ARE)-driven luciferase activity in Raw264.7 cells transfected with an ARE-luciferase reporter construct containing the enhancer 2 and minimal promoter region of HO-1. These results suggest that piceatannol exerts anti-inflammatory effects via the down-regulation of iNOS expression and up-regulation of HO-1 expression.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.336-342
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• 2008

The resveratrol analogue piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine and reported to have anti-carcinogenic activities. To investigate the mechanism of anticarcinogenic activities of piceatannol, the effects on CYP 1 enzymes were determined in Escherichia coli membranes coexpressing recombinant human CYP1A1, CYP1A2 or CYP1B1 with human NADPH-P450 reductase. Piceatannol showed a strong inhibition of CYP1A1 and CYP1B1 in a concentration-dependent manner, and $IC_{50}$ of human CYP1A1 and CYP1B1 was 5.8 ${\mu}M$ and 16.6 ${\mu}M$, respectively. However, piceatannol did not inhibit CYP1A2 activity in the concentration of up to 100 ${\mu}M$. Piceatannol exhibited 3-fold selectivity for CYP1B1 over CYP1A1. The mode of inhibition of piceatannol was non-competitive for CYP1A1 and CYP1B1. The result that piceatannol did not inhibit CYP1B1-mediated $\alpha$-naphthoflavone ($\alpha$-NF) metabolism suggests piceatannol may act as a non-competitive inhibitor as well. In human prostate carcinoma PC-3 cells, piceatannol induces apoptosis and prevents Aktmediated signal pathway. Taken together, abilities of piceatannol to induce apoptotic cell death as well as CYP1 enzyme inhibition make this compound a useful tool for cancer chemoprevention.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.7
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• pp.975-982
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• 2015

Piceatannol (trans-3,4,3',5'-trihydroxystilbene), a natural stilbene, is an analogue of resveratrol. In the present study, possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human oral cancer YD-15 cells were investigated. To investigate whether or not piceatannol has effects on cancer cell viability, human oral YD-15 cells were treated with piceatannol (0, 50, and $100{\mu}M$). Piceatannol treatment ($100{\mu}M$) showed the strongest inhibition of cell proliferation and reduced cell viability in a dose-dependent manner. Chromatin condensation detected by DAPI staining significantly increased in a concentration-dependent manner, indicating apoptosis. Piceatannol treatment activated initiator Bax (pro-apoptotic) and cPARP in a concentration-dependent manner. Further, piceatannol induced down-regulation of Bcl-2 (anti-apoptotic). We also evaluated the activity of piceatannol against oral cavity cancer tumors in mice. Piceatannol-treated nude mice bearing YD-15 xenograft tumors exhibited significantly reduced tumor volume and weight due to the potent effect of piceatannol on tumor cell apoptosis, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Immunohistochemistry staining showed elevated expression of cleaved-caspase-3 as well as reduced expression of Ki-67 in the piceatannol-treated group. Therefore, piceatannol can be developed as a cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human oral cancer cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.7
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• pp.907-913
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• 2012

Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene) is a polyphenol detected in grapes, rhubarb, and sugarcane. Although recent experimental data revealed that this compound is known to exhibit immunosuppressive and antitumorigenic activities in several cell lines, the molecular mechanisms underlying anticancer activity are poorly understood. In the present study, we investigated possible further mechanisms by which piceatannol exerts its anti-proliferative action in cultured human gastric cancer AGS cells. Piceatannol treatment resulted in the inhibition of growth and G1 arrest of the cell cycle in a concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by piceatannol was associated with the modulation of cyclin-dependent kinases (Cdks) and cyclins, up-regulation of the expression of Cdk inhibitor p21 (WAF1/CIP1) in both transcriptional and translational levels, and the inhibition of phosphorylation of retinoblastoma proteins and E2F1 expression. In addition, piceatannol treatment caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin $E_2$ synthesis.

• Applied Biological Chemistry
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• v.44 no.3
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• pp.208-210
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• 2001

• Korean Journal of Pharmacognosy
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• v.31 no.2
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• pp.245-248
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• 2000

As a series of the studies on cultivated Korean rhubarb rhizomes (Rheum undulatum), five stilbene derivatives were screened for inhibitory activity against $5{\alpha}-reductase$. Of these, desoxyrhapontigenin, rhapontigenin, and piceatannol exhibited inhibition, whereas, two other stilbene glycosides, rhaponticin and $piceatannol-3'-O-{\beta}-D-glucopyranoside$ did not show the inhibition.

• Natural Product Sciences
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• v.13 no.4
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• pp.369-372
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• 2007

Oxidative stress induced by reactive oxygen species (ROS) has been suggested to be the cause of various degenerative diseases as well as aging. To evaluate the antioxidant potential of stilbenes, we have investigated the cytoprotective effect of 10 stilbenes derived from plants on the oxidative stress induced by tertiary butyl hydroperoxide (t-BuOOH). Of the stilbenes tested, piceatannol (3) showed the most potent activity, which was further investigated using an animal model. When 3 (30 or 10 mg/kg) was topically administered prior to UVB irradiation, the amount of the thiobarbituric acid reactive substances (TBARS) was significantly reduced compared to that of the control (vehicle). Our findings suggest that piceatannol is capable of protecting cells and tissues from oxidative stress.

• Korean Journal of Plant Resources
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• v.21 no.6
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• pp.431-434
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• 2008

Dental caries is the destruction of the enamel of teeth by Streptoccus mutans. S. mutans has been isolated from human dental plaque and is associated with the initial development of enamel lesions. We have studied the antibacterial action of the fruit of Callistemon citrin us against a cariogenic bacterium, S. mutans. From the fruit of C. citrinus, piceatannol (3,3',4',5-tetrahydroxystilbene) was isolated by repeated column chromatography with $SiO_2$ and Sephadex LH-20. Its structure was elucidated by instrumental analysis using 1D-NMR, 2D-NMR and EI-MS. This compound was isolated from the fruit of C. citrin us for the first time. The anticarcinogenic activity of this compound was determined by using agar well-diffusion method and minimal inhibition concentration (MIC).

• Archives of Pharmacal Research
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• v.23 no.2
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• pp.159-162
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• 2000

A new stilbene diglycoside, piceatannol-3, 4'-O-$\beta$-D-diglucopyranoside (I), together with desoxyrhaponticin (II), emodin-1-O-$\beta$-D-glucopyranoside (III), and physcion-8-O-b-D-gluco-pyranoside (IV), were isolated from the rhizomes of cultivated Korean rhubarb rhizomes(Rheum undulatum), Jong DaeWhang, and the structures of 1-IV were identified on the basis of chemical and spectral evidences.