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Ki Won Lee - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of tumor progression by oral Piceatannol in mouse 4T1 mammary cancer is associated with decreased angiogenesis and macrophage infiltration.
The Journal of nutritional biochemistry, 2015Co-Authors: Hye Rim Song, Jae In Jung, Song Her, Han Jin Cho, Seung-hae Kwon, Young-hee Kang, Ki Won Lee, Jung Han Yoon ParkAbstract:Piceatannol, a polyphenol which exhibits anticancer activities, is found in grapes, red wine and berries. It has been shown to inhibit several transcription factor pathways. The present study was conducted to determine whether oral administration of Piceatannol inhibits mammary tumor progression. 4T1 mammary carcinoma cells were injected into the mammary fat pad of syngeneic female BALB/c mice. Starting 1 day later, Piceatannol (10- or 20-mg/kg body weight/day) was administered by oral gavage for 30 days. Piceatannol treatment reduced tumor growth. In tumor tissues, Piceatannol treatment reduced the expression of transcription factors P-NFκB p65, P-STAT3 and HIF-1α and multiple proteins involved in regulation of cell cycle progression (Ki67, cyclin D1, cyclin A, CDK2, CDK4), angiogenesis (VEGF-A, VEGFR-2, VE-cadherin, CD31) and lymphangiogenesis (VEGF-C, LYVE-1), as well as macrophage infiltration. Piceatannol significantly increased apoptotic cells and expression of both Bax and cleaved caspase-3 but reduced Bcl-2 expression in tumor tissues. In addition, Piceatannol reduced the number and volume of pulmonary tumor nodules and expression of MMP-9 in both lung and tumor. It also reduced tissue levels of cytokines/chemokines, including M-CSF and MCP-1. In vitro results revealed that Piceatannol inhibited migration of 4T1 cells and monocytes, as well as secretion of MCP-1 and M-CSF by 4T1 cells. 4T1 cell-conditioned medium stimulated monocyte migration, which was suppressed by a CCR2 antibody. These results indicate that alteration in tumor microenvironment (macrophages, transcription factors, etc.) is an important mechanism by which Piceatannol inhibits tumor proliferation, angiogenesis and lymphangiogenesis, leading to suppression of mammary tumor growth and metastasis.
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Piceatannol suppresses the metastatic potential of mcf10a human breast epithelial cells harboring mutated h ras by inhibiting mmp 2 expression
International Journal of Molecular Medicine, 2013Co-Authors: Nu Ry Song, Ki Won Lee, Mun Kyung Hwang, Yongseok Heo, Hyong Joo LeeAbstract:Metastasis is one of the most threatening features of the oncogenic process and the main cause of cancer-related mortality. Several studies have demonstrated that matrix metalloproteinases (MMPs) are critical for tumor invasion and metastasis. Resveratrol (3,5,4'-trihydroxystilbene), a phenolic compound of red wine, has been reported to be a natural chemopreventive agent. However, the cancer preventive effects of Piceatannol (3,5,3',4'-tetrahydroxystilbene), a metabolite of resveratrol and the underlying molecular mechanisms have not yet been fully elucidated. In this study, we report that Piceatannol inhi-bits H-ras-induced MMP-2 activity and the invasive phenotype of MCF10A human breast epithelial cells harboring mutated H-ras (H-ras MCF10A cells) more effectively than resveratrol. Piceatannol attenuated the H-ras-induced phosphorylation of Akt in a time- and dose-dependent manner, whereas resveratrol, at the same concentrations, did not exert an inhibitory effect. In vitro kinase assays demonstrated that Piceatannol significantly inhibited phosphatidylinositol 3-kinase (PI3K) activity and suppressed phospha-tidylinositol (3,4,5)-trisphosphate (PIP3) expression in the H-ras MCF10A cells. Ex vivo pull-down assays revealed that Piceatannol directly bound to PI3K, inhibiting PI3K activity. Data from molecular docking suggested that Piceatannol is a more tight-binding inhibitor than resveratrol due to the additional hydrogen bond between the hydroxyl group and the backbone amide group of Val882 in the ATP-binding pocket of PI3K.
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phosphoinositide 3 kinase is a novel target of Piceatannol for inhibiting pdgf bb induced proliferation and migration in human aortic smooth muscle cells
Cardiovascular Research, 2010Co-Authors: Keun Hwa Choi, Jong-eun Kim, Nu Ry Song, Joe Eun Son, Mun Kyung Hwang, Sanguine Byun, Jong Hun Kim, Ki Won LeeAbstract:Aims Abnormal migration and proliferation of human aortic smooth muscle cells (HASMCs) to the intima causes intimal thickening of the aorta, which is strongly related to the development of atherosclerosis. Previous studies have suggested that red wine polyphenols, particularly resveratrol, have great protective effects against cardiovascular diseases. Here, we compared the anti-atherosclerotic effect of Piceatannol, a metabolite of resveratrol, and its underlying mechanisms. Methods and results We demonstrated that Piceatannol inhibited platelet-derived growth factor (PDGF)-BB-induced cell migration using a modified Boyden chamber assay and wound healing assay. Western blot analysis showed that PDGF-BB-induced phosphorylation of Akt, p70S6K, and p38 was inhibited by Piceatannol, but not resveratrol. In vitro and ex vivo phosphoinositide 3-kinase (PI3K) assays demonstrated that Piceatannol suppressed PI3K activity more effectively than resveratrol. PDGF-BB-induced migration and proliferation of HASMCs were inhibited by treatment with a commercial PI3K inhibitor, LY294002. Both in vitro and ex vivo pull-down assays revealed that Piceatannol directly binds with sepharose 4B-PI3K beads in an ATP-competitive manner. Conclusion The results of the present study demonstrate that Piceatannol directly binds with PI3K in an ATP-competitive manner and suppresses PI3K activity with anti-atherosclerotic effects.
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Piceatannol Attenuates 4-Hydroxynonenal-Induced Apoptosis of PC12 Cells by Blocking Activation of c-Jun N-Terminal Kinase
Annals of the New York Academy of Sciences, 2009Co-Authors: Young Jin Jang, Ki Won Lee, Jong-eun Kim, Nam Joo Kang, Hyong Joo LeeAbstract:Alzheimer's disease (AD) is an age-related neurodegenerative disorder in which apoptosis plays a potentially important role. 4-Hydroxynonenal (HNE) is a major lipid peroxidation product produced by oxidative stress, and its level is elevated in the AD brain. In the present study, Piceatannol (but not resveratrol) at the concentration of 20 micromol/L inhibited HNE-induced PC12 cell death. Treatment with HNE induced nuclear condensation in PC12 cells, and this was attenuated by Piceatannol treatment. HNE induced poly(ADP-ribose) polymerase cleavage and decreased Bcl-2 expression, with both of these effects being attenuated by Piceatannol. Piceatannol also inhibited the phosphorylation of c-Jun N-terminal kinase, which is a key regulator of HNE-induced PC12 cell death. These results indicate that Piceatannol has therapeutic potential in the prevention of AD.
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Protective effects of Piceatannol against beta-amyloid-induced neuronal cell death.
Annals of the New York Academy of Sciences, 2007Co-Authors: Hyo Jin Kim, Ki Won Lee, Hyong Joo LeeAbstract:Beta-amyloid (Abeta) is a main component of senile plaques in Alzheimer's disease (AD) that induces neuronal cell death. Since reactive oxygen species (ROS) have been implicated in Abeta-induced neurotoxicity, considerable attention has recently been focused on identifying naturally occurring antioxidative phenolic phytochemicals that are able to decrease ROS levels. Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene), which has a structure homologous to resveratrol, is an anti-inflammatory and antiproliferative stilbene compound derived from plants. This article investigated the possible protective effects of Piceatannol on Abeta-induced PC12 neuronal cell death, and found that Piceatannol exerted much stronger protective effects than did resveratrol. Piceatannol treatment attenuated the intracellular accumulation of ROS induced by treatment of PC12 cells with Abeta, inhibited Abeta-induced apoptotic features including internucleosomal DNA fragmentation, nucleus condensation, cleavage of poly(ADP-ribose) polymerase (PARP), and activation of caspase-3. These results suggest that Piceatannol blocks Abeta-induced accumulation of ROS, thereby protecting PC12 cells from oxidative stress.
Tatsuhiko Ito - One of the best experts on this subject based on the ideXlab platform.
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Piceatannol is superior to resveratrol in promoting neural stem cell differentiation into astrocytes
Food & function, 2016Co-Authors: Daisuke Arai, Tatsuhiko Ito, Hiroko Maruki-uchida, Sai Masahiko, Ryousuke Kataoka, Satoshi Otsuka, Midori Kawamura, Youichi NakaoAbstract:Piceatannol (3,3′,4′,5-trans-tetrahydroxystilbene) is a polyphenolic compound abundant in the seeds of passion fruit (Passiflora edulis). Piceatannol is an analogue of resveratrol (3,4′,5-trans-trihydroxystilbene) and shares the structural motif and biological activities such as activation of SIRT1. Several studies have shown that Piceatannol is more potent than resveratrol. In this study, we examined the effects of Piceatannol on neural stem cell differentiation into astrocytes compared with those of resveratrol. At a concentration of 2.5 μM, Piceatannol promoted astrocyte differentiation, while resveratrol had no effect at this concentration. Furthermore, we found that oral administration of Piceatannol increased the number of astrocytes in the brains of adult mice, while resveratrol administration showed no effects. These results suggest that Piceatannol has a superior effect to resveratrol in promoting astrocyte differentiation.
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Administration of Piceatannol Complexed with α-Cyclodextrin Improves Its Absorption in Rats.
Journal of agricultural and food chemistry, 2016Co-Authors: Hiroyuki Inagaki, Ryouichi Ito, Yuko Setoguchi, Yukihiro Oritani, Tatsuhiko ItoAbstract:Piceatannol is polyphenolic antioxidant found in passion fruit (Passiflora edulis) seeds. The aim of this study was to improve the absorption of Piceatannol using α-cyclodextrin (αCD). The solubility of Piceatannol in neutral and acidic solutions increased in an αCD concentration-dependent manner. The maximum plasma concentration of intact Piceatannol and the time-to-maximum plasma concentration of O-methylated Piceatannol metabolites increased in rats administered αCD–Piceatannol inclusion complexes (PICs). Administering the αCD inclusion complexes significantly increased the area under the concentration–time curve of total stilbene derivatives (0–3 h) in terms of the total amount of intact Piceatannol, O-methylated Piceatannol, conjugated Piceatannol, and isorhapontigenin. Gastrointestinal ligation experiments demonstrated that substantially higher levels of Piceatannol metabolites were present in the lower intestine (the ileum) at 1 h postintragastric αCD–PICs administration as compared to those observ...
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Enhanced glucose tolerance by intravascularly administered Piceatannol in freely moving healthy rats.
Biochemical and biophysical research communications, 2016Co-Authors: Yukihiro Oritani, Tatsuhiko Ito, Sai Masahiko, Teru Okitsu, Eisaku Nishimura, Shoji TakeuchiAbstract:Piceatannol is a phytochemical in the seeds of passion fruit that has a hypoglycemic effect when orally administered. To elucidate the contribution of intact and metabolites of Piceatannol after gastro-intestinal absorption to hypoglycemic effect, we examined the influence of Piceatannol and isorhapontigenin on blood glucose concentrations during fasting and glucose tolerance tests by administering them intravascularly to freely moving healthy rats. We found that intravascularly administered Piceatannol reduced the blood glucose concentrations during both fasting and glucose tolerance tests, but isorhapontigenin did not during either of them. Furthermore, we found that Piceatannol increased the insulinogenic index during glucose tolerance tests and that Piceatannol had no influence on insulin sensitivity by performing hyperinsulinemic euglycemic clamping tests. These results suggest that Piceatannol orally intaken may enhance glucose tolerance by the effect of intact Piceatannol through enhanced early-phase secretion of insulin. Therefore, oral intake of Piceatannol might contribute to proper control of postprandial glycemic excursions in healthy subjects.
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Piceatannol Lowers the Blood Glucose Level in Diabetic Mice
Biological & pharmaceutical bulletin, 2015Co-Authors: Hiroko Uchida-maruki, Ikuko Kurita, Hiroyuki Inagaki, Ryouichi Ito, Sai Masahiko, Tatsuhiko ItoAbstract:We previously found that passion fruit (Passiflora edulis) seeds contained a high amount of Piceatannol (3,5,3',4'-trans-tetrahydroxystilbene), a natural analog of resveratrol (3,5,4'-trans-trihydroxystilbene). Resveratrol has been proposed as a potential anti-metabolic disorder compound, by its activation of sirtuin and AMP-activated protein kinase. Many reports show that resveratrol ameliorates diet-induced obesity and insulin resistance. However, it is not known whether Piceatannol also affects diet-induced obesity. We explored the effect of Piceatannol on high fat diet-fed mice. The results showed that Piceatannol did not affect high fat diet-induced body weight gain or visceral fat gain in mice. However, Piceatannol did reduce fasting blood glucose levels. Furthermore, to explore the potential of passion fruit seed extract containing Piceatannol as a functional food, passion fruit seed extract was administered in a genetic diabetic mouse model (db/db mice). Single administration of passion fruit seed extract, as well as Piceatannol reduced the blood glucose levels of these db/db mice. These results suggest that Piceatannol and passion fruit seed extract may have potential application in the prevention of diabetes.
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Piceatannol and Its Metabolite, Isorhapontigenin, Induce SIRT1 Expression in THP-1 Human Monocytic Cell Line
Nutrients, 2014Co-Authors: Shinpei Kawakami, Hiroko Maruki-uchida, Yosuke Kinoshita, Koji Yanae, Sai Masahiko, Tatsuhiko ItoAbstract:Piceatannol is a phytochemical that is present in large amounts in passion fruit (Passiflora edulis) seeds, and is an analog of resveratrol. Recently, the absorption and metabolism of Piceatannol were investigated in rats, and isorhapontigenin, O-methyl Piceatannol, was detected as a Piceatannol metabolite in rat plasma. To elucidate the function of Piceatannol and its metabolites, we investigated the expression of sirtuin 1 (SIRT1) in THP-1 monocytic cells after treatment with Piceatannol and its metabolites, and compared their effects with those of resveratrol and its metabolites. Piceatannol and resveratrol upregulated the expression levels of SIRT1 mRNA and SIRT1 protein. An extract of passion fruit seeds, which contained high levels of Piceatannol, also upregulated SIRT1 mRNA expression. As for the metabolites, isorhapontigenin upregulated SIRT1 mRNA expression, whereas resveratrol glucuronides and sulfate did not affect SIRT1 expression. These findings indicate that after intake of Piceatannol, not only Piceatannol itself, but also its metabolite, isorhapontigenin, contributed to the upregulation of SIRT1 expression.
Jung Han Yoon Park - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of tumor progression by oral Piceatannol in mouse 4T1 mammary cancer is associated with decreased angiogenesis and macrophage infiltration.
The Journal of nutritional biochemistry, 2015Co-Authors: Hye Rim Song, Jae In Jung, Song Her, Han Jin Cho, Seung-hae Kwon, Young-hee Kang, Ki Won Lee, Jung Han Yoon ParkAbstract:Piceatannol, a polyphenol which exhibits anticancer activities, is found in grapes, red wine and berries. It has been shown to inhibit several transcription factor pathways. The present study was conducted to determine whether oral administration of Piceatannol inhibits mammary tumor progression. 4T1 mammary carcinoma cells were injected into the mammary fat pad of syngeneic female BALB/c mice. Starting 1 day later, Piceatannol (10- or 20-mg/kg body weight/day) was administered by oral gavage for 30 days. Piceatannol treatment reduced tumor growth. In tumor tissues, Piceatannol treatment reduced the expression of transcription factors P-NFκB p65, P-STAT3 and HIF-1α and multiple proteins involved in regulation of cell cycle progression (Ki67, cyclin D1, cyclin A, CDK2, CDK4), angiogenesis (VEGF-A, VEGFR-2, VE-cadherin, CD31) and lymphangiogenesis (VEGF-C, LYVE-1), as well as macrophage infiltration. Piceatannol significantly increased apoptotic cells and expression of both Bax and cleaved caspase-3 but reduced Bcl-2 expression in tumor tissues. In addition, Piceatannol reduced the number and volume of pulmonary tumor nodules and expression of MMP-9 in both lung and tumor. It also reduced tissue levels of cytokines/chemokines, including M-CSF and MCP-1. In vitro results revealed that Piceatannol inhibited migration of 4T1 cells and monocytes, as well as secretion of MCP-1 and M-CSF by 4T1 cells. 4T1 cell-conditioned medium stimulated monocyte migration, which was suppressed by a CCR2 antibody. These results indicate that alteration in tumor microenvironment (macrophages, transcription factors, etc.) is an important mechanism by which Piceatannol inhibits tumor proliferation, angiogenesis and lymphangiogenesis, leading to suppression of mammary tumor growth and metastasis.
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Piceatannol inhibits migration and invasion of prostate cancer cells: possible mediation by decreased interleukin-6 signaling.
The Journal of nutritional biochemistry, 2011Co-Authors: Gyoo Taik Kwon, Jong-gab Jun, Jae In Jung, Hye Rim Song, Eun Young Woo, Jin-kyung Kim, Song Her, Jung Han Yoon ParkAbstract:Piceatannol (trans-3,4,3′,5′-tetrahydroxystilbene) is a polyphenol detected in grapes, red wine and Rheum undulatum; it has also been demonstrated to exert anticarcinogenic effects. In this study, in order to determine whether Piceatannol inhibits the lung metastasis of prostate cancer cells, MAT-Ly-Lu (MLL) rat prostate cancer cells expressing luciferase were injected into the tail veins of male nude mice. The oral administration of Piceatannol (20 mg/kg) significantly inhibited the accumulation of MLL cells in the lungs of these mice. In the cell culture studies, Piceatannol was demonstrated to inhibit the basal and epidermal growth factor (EGF)-induced migration and invasion of DU145 cells, in addition to the migration of MLL, PC3 and TRAMP-C2 prostate cancer cells. In DU145 cells, Piceatannol attenuated the secretion and messenger RNA levels of matrix metalloproteinase-9, urokinase-type plasminogen activator (uPA) and vascular endothelial growth factor (VEGF). Piceatannol increased the protein levels of tissue inhibitor of metalloproteinase-2 in a concentration-dependent fashion. Additionally, Piceatannol inhibited the phosphorylation of signal transducer and activator of transcription (STAT) 3. Furthermore, Piceatannol effected reductions in both basal and EGF-induced interleukin (IL)-6 secretion. An IL-6 neutralizing antibody inhibited EGF-induced STAT3 phosphorylation and EGF-stimulated migration of DU145 cells. Interleukin-6 treatment was also shown to enhance the secretion of uPA and VEGF, STAT3 phosphorylation and the migration of DU145 cells; these increases were suppressed by Piceatannol. These results demonstrate that the inhibition of IL-6/STAT3 signaling may constitute a mechanism by which Piceatannol regulates the expression of proteins involved in regulating the migration and invasion of DU145 cells.
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Abstract 1460: Piceatannol suppresses the migration and invasion of DU145 human prostate cancer cells
Tumor Biology, 2010Co-Authors: Gyoo Taik Kwon, Jin-kyung Kim, Jung Han Yoon ParkAbstract:Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Piceatannol (trans-3,4,3′,5′-tetrahydroxystilbene) is a polyphenol found in grapes, red wine, Rheum undulatum and seeds of Euphorbia lagascae. The purpose of the present study was to investigate the effects of Piceatannol on the migration and invasion characteristics of DU145 prostate cancer cells. DU145 cells were cultured in the presence of 0 − 10 μmol/L Piceatannol with or without 10 μg/L epidermal growth factor (EGF). Piceatannol inhibited the basal and EGF-induced cell migration and invasion of DU145 cells. Gelatin zymography and Western blot analysis, Fibrin zymography and real time RT-PCR analysis were conducted using conditioned media and cell extracts. Piceatannol reduced the secretion and mRNA levels of matrix metalloproteinase (MMP)-9, urokinase-type plasminogen activator (uPA), and vascular endothelial growth factor (VEGF). Piceatannol decreased the protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 but increased TIMP-2 levels in a concentration-dependent manner. Additionally, Piceatannol inhibited the phosphorylation of signal transducer and activator of transcription (STAT)3. Furthermore, Piceatannol decreased both basal and EGF-induced secretion of IL-6. IL-6 treatment increased the secretion of uPA and VEGF, the phosphorylation of STAT3, and migration of DU145 cells and these increase were suppressed by Piceatannol. An IL-6 nutralizing antibody inhibited the EGF-induced phosphorylation of STAT3 and increase in cell migration and invasion of DU145 cells, which may be mediated via the inhibition of MMP-9 and uPA activities and secretion of VEGF. The inhibition of IL-6/STAT3 activation may be one of the mechanisms by which Piceatannol regulates the expression of proteins involved in the rehulation of DU145 cell migration and invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1460.
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Piceatannol a natural stilbene from grapes induces g1 cell cycle arrest in androgen insensitive du145 human prostate cancer cells via the inhibition of cdk activity
Cancer Letters, 2009Co-Authors: Yeo Myeong Lee, Jin-kyung Kim, Do Young Lim, Han Jin Cho, Mi Ra Seon, Booyong Lee, Jung Han Yoon ParkAbstract:Abstract We have examined whether and by what mechanism Piceatannol inhibits cell cycle progression in DU145 cells. The treatment of cells with Piceatannol for 24 h resulted in an increase in the percentage of cells in G1 phase and dose-dependent decreases in [3H]thymidine incorporation, as well as in protein levels of cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 and CDK4. Piceatannol exerted no effect on the levels of p21WAF1/CIP1 or p27KIP1. Piceatannol reduced CDK4 and CDK2 activity. These results indicate that delaying G1 cell cycle progression contributes to the Piceatannol-mediated inhibition of DU145 cell growth, which may be mediated via the inhibition of CDK activity.
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The grape component Piceatannol induces apoptosis in DU145 human prostate cancer cells via the activation of extrinsic and intrinsic pathways.
Journal of medicinal food, 2009Co-Authors: Eun Ji Kim, Heesook Park, Soyoung Park, Jong-gab Jun, Jung Han Yoon ParkAbstract:Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene) is a polyphenol that is found in grapes, red wine, Rheum undulatum, and the seeds of Euphorbia lagascae. It has been previously reported that Piceatannol inhibits the proliferation of a variety of cancer cell types. In the present study, we assessed the effects of Piceatannol on the growth of androgen-insensitive DU145 prostate cancer cells at concentrations of 1-10 micromol/L. Piceatannol reduced the viable numbers and increased the numbers of apoptotic DU145 cells in a dose-dependent manner. Western blot analysis revealed that Piceatannol increased the protein levels of cleaved caspase-8, -9, -7, and -3 and cleaved poly(ADP-ribose) polymerase (PARP). Piceatannol increased mitochondrial membrane permeability and cytochrome c release from the mitochondria to the cytosol. Piceatannol induced an increase in the levels of truncated Bid, Bax, Bik, Bok, and Fas but caused a decrease in the levels of Mcl-1 and Bcl-xL. Caspase-8 and -9 inhibitors mitigated Piceatannol-induced apoptosis. The caspase-8 inhibitor suppressed the Piceatannol-induced cleavage of Bid, caspase-3, and PARP. These results indicate that Piceatannol induces apoptosis via the activation of the death receptor and mitochondrial-dependent pathways in prostate cancer cells.
Kazumi Yagasaki - One of the best experts on this subject based on the ideXlab platform.
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Piceatannol a resveratrol derivative promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in l6 myocytes and suppresses blood glucose levels in type 2 diabetic model db db mice
Biochemical and Biophysical Research Communications, 2012Co-Authors: Miki Minakawa, Yutaka Miura, Kazumi YagasakiAbstract:Abstract The skeletal muscle cells are one of the main sites of glucose uptake through glucose transporter 4 (GLUT4) in response to insulin. In muscle cells, 5′ adenosine monophosphate-activated protein kinase (AMPK) is known as another GLUT4 translocation promoter. Natural compounds that activate AMPK have a possibility to overcome insulin resistance in the diabetic state. Piceatannol is a natural analog and a metabolite of resveratrol, a known AMPK activator. In this study, we investigate the in vitro effect of Piceatannol on glucose uptake, AMPK phosphorylation and GLUT4 translocation to plasma membrane in L6 myocytes, and its in vivo effect on blood glucose levels in type 2 diabetic model db/db mice. Piceatannol was found to promote glucose uptake, AMPK phosphorylation and GLUT4 translocation by Western blotting analyses in L6 myotubes under a condition of insulin absence. Promotion by Piceatannol of glucose uptake as well as GLUT4 translocation to plasma membrane by immunocytochemistry was also demonstrated in L6 myoblasts transfected with a glut4 cDNA-coding vector. Piceatannol suppressed the rises in blood glucose levels at early stages and improved the impaired glucose tolerance at late stages in db/db mice. These in vitro and in vivo findings suggest that Piceatannol may be preventive and remedial for type 2 diabetes and become an antidiabetic phytochemical.
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Antiproliferative and Anti-Invasive Effect of Piceatannol, a Polyphenol Present in Grapes and Wine, against Hepatoma AH109A Cells
Journal of biomedicine & biotechnology, 2012Co-Authors: Yuichiro Kita, Yutaka Miura, Kazumi YagasakiAbstract:Piceatannol is a stilbenoid, a metabolite of resveratrol found in red wine. Piceatannol and sera from rats orally given Piceatannol were found to dose-dependently suppress both the proliferation and invasion of AH109A hepatoma cells in culture. Its antiproliferative effect was based on cell cycle arrest at lower concentration (25~50 μM) and on apoptosis induction at higher concentration (100 μM). Piceatannol suppressed reactive oxygen species-potentiated invasive capacity by scavenging the intracellular reactive oxygen species. These results suggest that Piceatannol, unlike resveratrol, has a potential to suppress the hepatoma proliferation by inducing cell cycle arrest and apoptosis induction. They also suggest that the antioxidative property of Piceatannol, like resveratrol, may be involved in its anti-invasive action. Subsequently, Piceatannol was found to suppress the growth of solid tumor and metastasis in hepatoma-bearing rats. Thus, Piceatannol may be a useful anticancer natural product.
Dan Weng - One of the best experts on this subject based on the ideXlab platform.
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Piceatannol attenuates d galn lps induced hepatoxicity in mice involvement of er stress inflammation and oxidative stress
International Immunopharmacology, 2018Co-Authors: Jingjing Wen, Hongfa Lin, Mengshu Zhao, Liang Tao, Yunxia Yang, Aiqun Jia, Jianfa Zhang, Dan WengAbstract:Piceatannol, a natural derivative of resveratrol, has been shown to exert similar anti-oxidant and anti-inflammatory effects as resveratrol. However, it remains unknown whether Piceatannol has hepatoprotective effect against acute liver injury. In this study, we investigated the in vivo effect of Piceatannol on D-GalN/LPS-induced fulminant hepatic failure (FHF), and its in vitro effect on ER stress-inducing drug thapsigargin (TG)-induced proinflammatory cytokines production and ROS release. Our results indicated that Piceatannol markedly decreased the mortality rate, reduced the serum levels of alanine transaminase and aspartic aminotransferase, ameliorated the liver damage induced by D-GalN/LPS in mice. In addition, Piceatannol reduced the expression of proinflammatory cytokines, including TNF-α, IL-1β and IL-6, the expression of ER stress markers CHOP and phosphorylated-IRE1α, and the generation of oxidative stress in D-GalN/LPS-treated mouse liver. In vitro results were consistent with in vivo observations, demonstrating that Piceatannol suppressed the secretion of proinflammatory cytokines, inflammasome activation and the production of ROS induced by TG with or without LPS priming in J774A.1 macrophages. Our study proposes Piceatannol as a promising medication for preventing acute liver failure and the mechanisms may be related to its inhibitory effects on ER stress, inflammation and oxidative stress.
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Piceatannol attenuates D-GalN/LPS-induced hepatoxicity in mice: Involvement of ER stress, inflammation and oxidative stress.
International immunopharmacology, 2018Co-Authors: Jingjing Wen, Hongfa Lin, Mengshu Zhao, Liang Tao, Yunxia Yang, Aiqun Jia, Jianfa Zhang, Dan WengAbstract:Piceatannol, a natural derivative of resveratrol, has been shown to exert similar anti-oxidant and anti-inflammatory effects as resveratrol. However, it remains unknown whether Piceatannol has hepatoprotective effect against acute liver injury. In this study, we investigated the in vivo effect of Piceatannol on D-GalN/LPS-induced fulminant hepatic failure (FHF), and its in vitro effect on ER stress-inducing drug thapsigargin (TG)-induced proinflammatory cytokines production and ROS release. Our results indicated that Piceatannol markedly decreased the mortality rate, reduced the serum levels of alanine transaminase and aspartic aminotransferase, ameliorated the liver damage induced by D-GalN/LPS in mice. In addition, Piceatannol reduced the expression of proinflammatory cytokines, including TNF-α, IL-1β and IL-6, the expression of ER stress markers CHOP and phosphorylated-IRE1α, and the generation of oxidative stress in D-GalN/LPS-treated mouse liver. In vitro results were consistent with in vivo observations, demonstrating that Piceatannol suppressed the secretion of proinflammatory cytokines, inflammasome activation and the production of ROS induced by TG with or without LPS priming in J774A.1 macrophages. Our study proposes Piceatannol as a promising medication for preventing acute liver failure and the mechanisms may be related to its inhibitory effects on ER stress, inflammation and oxidative stress.