Resveratrol and its analogs: Defense against cancer, coronary disease and neurodegenerative maladies or just a fad?

Mutation Research/Reviews in Mutation Research - Tập 658 Số 1-2 - Trang 68-94 - 2008
Thomas Szekeres1, Akos Szakmary2, Walter Jäger3
1Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, General Hospital of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria
2Department of Medicine I, Division of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria
3Department of Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria

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Baur, 2006, Therapeutic potential of resveratrol: the in vivo evidence, Nat. Rev. Drug Discov., 5, 493, 10.1038/nrd2060

Langcake, 1976, The production of resveratrol by Vitis vinifera and other members of the Vitaceae as a response to infection or injury, Physiol. Plant Pathol., 9, 77, 10.1016/0048-4059(76)90077-1

Burns, 2002, Plant foods and herbal sources of resveratrol, J. Agric. Food Chem., 50, 3337, 10.1021/jf0112973

Nonomura, 1963, Chemical Constituents Of Polygonaceous Plants. I. Studies On The Components Of Ko-J O-Kon (Polygonum Cuspidatum Sieb. Et Zucc.), Yakugaku Zasshi, 83, 988, 10.1248/yakushi1947.83.10_988

Soleas, 1997, Resveratrol: a molecule whose time has come? And gone?, Clin. Biochem., 30, 91, 10.1016/S0009-9120(96)00155-5

Siemann, 1992, Concentration of phytoalexin resveratrol in wine, Am. J. Enol. Vitic., 43, 49, 10.5344/ajev.1992.43.1.49

Creasy, 1988, Phytoalexin production potential of grape berries, J. Am. Soc. Hortic. Sci., 113, 230, 10.21273/JASHS.113.2.230

Gusman, 2001, A reappraisal of the potential chemopreventive and chemotherapeutic properties of resveratrol, Carcinogenesis, 22, 1111, 10.1093/carcin/22.8.1111

Renaud, 1992, alcohol, platelets, and the French paradox for coronary heart disease, Lancet, 339, 1523, 10.1016/0140-6736(92)91277-F

Hao, 2004, Mechanisms of cardiovascular protection by resveratrol, J. Med. Food, 7, 290, 10.1089/jmf.2004.7.290

Dong, 2003, Molecular mechanism of the chemopreventive effect of resveratrol, Mutat. Res., 523/524, 145, 10.1016/S0027-5107(02)00330-5

Hursting, 1999, Mechanism-based cancer prevention approaches: targets, examples, and the use of transgenic mice, J. Natl. Cancer Inst., 91, 215, 10.1093/jnci/91.3.215

Aggarwal, 2006, Molecular targets of dietary agents for prevention and therapy of cancer, Biochem. Pharmacol., 71, 1397, 10.1016/j.bcp.2006.02.009

Jang, 1997, Cancer chemopreventive activity of resveratrol: a natural product derived from grapes, Science, 275, 218, 10.1126/science.275.5297.218

Stewart, 2000, Effects of resveratrol on the autophosphorylation of phorbol ester-responsive protein kinases: inhibition of protein kinase D but not protein kinase C isozyme autophosphorylation, Biochem. Pharmacol., 60, 1355, 10.1016/S0006-2952(00)00450-0

Stewart, 1999, Resveratrol preferentially inhibits protein kinase C-catalyzed phosphorylation of a cofactor-independent, arginine-rich protein substrate by a novel mechanism, Biochemistry, 38, 13244, 10.1021/bi990875u

Bhat, 2001, Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models, Cancer Res., 61, 7456

Gehm, 1997, Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor, Proc. Natl. Acad. Sci. U.S.A., 94, 14138, 10.1073/pnas.94.25.14138

Mitchell, 1999, Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells, Cancer Res., 59, 5892

Stojanovic, 2001, Efficiency and mechanism of the antioxidant action of trans-resveratrol and its analogues in the radical liposome oxidation, Arch. Biochem. Biophys., 391, 79, 10.1006/abbi.2001.2388

Elford, 1970, Ribonucleotide reductase and cell proliferation. I. Variations of ribonucleotide reductase activity with tumor growth rate in a series of rat hepatomas, J. Biol. Chem., 245, 5228, 10.1016/S0021-9258(18)62745-0

Fontecave, 1998, Resveratrol: a remarkable inhibitor of ribonucleotide reductase, FEBS Lett., 421, 277, 10.1016/S0014-5793(97)01572-X

Locatelli, 2005, Inhibition of mammalian DNA polymerases by resveratrol: mechanism and structural determinants, Biochem. J., 389, 259, 10.1042/BJ20050094

Ragione, 1998, Resveratrol arrests the cell division cycle at S/G2 phase transition, Biochem. Biophys. Res. Commun., 250, 53, 10.1006/bbrc.1998.9263

Damianaki, 2000, Potent inhibitory action of red wine polyphenols on human breast cancer cells, J. Cell. Biochem., 78, 429, 10.1002/1097-4644(20000901)78:3<429::AID-JCB8>3.0.CO;2-M

Gautam, 2000, Resveratrol selectively inhibits leukemia cells: a prospective agent for ex vivo bone marrow purging, Bone Marrow Transplant., 25, 639, 10.1038/sj.bmt.1702189

Pozo-Guisado, 2002, The antiproliferative activity of resveratrol results in apoptosis in MCF-7 but not in MDA-MB-231 human breast cancer cells: cell-specific alteration of the cell cycle, Biochem. Pharmacol., 64, 1375, 10.1016/S0006-2952(02)01296-0

Schneider, 2000, Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells, Cancer Lett., 158, 85, 10.1016/S0304-3835(00)00511-5

Zhou, 2003, Resveratrol induces apoptosis in human esophageal carcinoma cells, World J. Gastroenterol., 9, 408, 10.3748/wjg.v9.i3.408

Delmas, 2002, Resveratrol, a chemopreventive agent, disrupts the cell cycle control of human SW480 colorectal tumor cells, Int. J. Mol. Med., 10, 193

Milner, 2001, Molecular targets for nutrients involved with cancer prevention, Nutr. Cancer, 41, 1

Horvath, 2005, Synergistic action of resveratrol, an ingredient of wine, with Ara-C and tiazofurin in HL-60 human promyelocytic leukemia cells, Exp. Hematol., 33, 329, 10.1016/j.exphem.2004.11.009

Lu, 2001, Resveratrol analog, 3, 4,5,4′-tetrahydroxystilbene, differentially induces pro-apoptotic p53/Bax gene expression and inhibits the growth of transformed cells but not their normal counterparts, Carcinogenesis, 22, 321, 10.1093/carcin/22.2.321

Ferry-Dumazet, 2002, Resveratrol inhibits the growth and induces the apoptosis of both normal and leukemic hematopoietic cells, Carcinogenesis, 23, 1327, 10.1093/carcin/23.8.1327

Schmitt, 2002, Hormonal and genotoxic activity of resveratrol, Toxicol. Lett., 136, 133, 10.1016/S0378-4274(02)00290-4

Matsuoka, 2001, Resveratrol, a naturally occurring polyphenol, induces sister chromatid exchanges in a Chinese hamster lung (CHL) cell line, Mutat. Res., 494, 107, 10.1016/S1383-5718(01)00184-X

Matsuoka, 2002, The 4’-hydroxy group is responsible for the in vitro cytogenetic activity of resveratrol, Mutat. Res., 521, 29, 10.1016/S1383-5718(02)00211-5

Horn, 2007, Oncogenicity evaluation of resveratrol in p53(+/−) (p53 knockout) mice, Food Chem. Toxicol., 45, 55, 10.1016/j.fct.2006.07.015

Halliwell, 1999

Packer, 1992, Interactions among antioxidants in health and disease: vitamin E and its redox cycle, Proc. Soc. Exp. Biol. Med., 200, 271, 10.3181/00379727-200-43433

Esterbauer, 1992, The role of lipid peroxidation and antioxidants in oxidative modification of LDL, Free Radic. Biol. Med., 13, 341, 10.1016/0891-5849(92)90181-F

Steinberg, 1989, Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity, N. Engl. J. Med., 320, 915

Whitehead, 1995, Effect of red wine ingestion on the antioxidant capacity of serum, Clin. Chem., 41, 32, 10.1093/clinchem/41.1.32

Fuhrman, 1995, Consumption of red wine with meals reduces the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation, Am. J. Clin. Nutr., 61, 549, 10.1093/ajcn/61.3.549

Miller, 1995, Antioxidant activity of resveratrol in red wine, Clin. Chem., 41, 1789, 10.1093/clinchem/41.12.1789

Frankel, 1993, Inhibition of human LDL oxidation by resveratrol, Lancet, 341, 1103, 10.1016/0140-6736(93)92472-6

Goldberg, 1995, Beyond alcohol: beverage consumption and cardiovascular mortality, Clin. Chim. Acta, 237, 155, 10.1016/0009-8981(95)06069-P

Wilson, 1996, Resveratrol promotes atherosclerosis in hypercholesterolemic rabbits, Life Sci., 59, PL15, 10.1016/0024-3205(96)00260-3

Li, 2006, Upregulation of endogenous antioxidants and phase 2 enzymes by the red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stress, Pharmacol. Res., 53, 6, 10.1016/j.phrs.2005.08.002

Hebbar, 2005, Toxicogenomics of resveratrol in rat liver, Life Sci., 76, 2299, 10.1016/j.lfs.2004.10.039

Dore, 2002, Decreased activity of the antioxidant heme oxygenase enzyme: implications in ischemia and in Alzheimer's disease, Free Radic. Biol. Med., 32, 1276

Kim, 2006, CO as a cellular signaling molecule, Annu. Rev. Pharmacol. Toxicol., 46, 411, 10.1146/annurev.pharmtox.46.120604.141053

Zhuang, 2003, Potential mechanism by which resveratrol, a red wine constituent, protects neurons, Ann. N. Y. Acad. Sci., 993, 276, 10.1111/j.1749-6632.2003.tb07534.x

Juan, 2005, Mechanism of concentration-dependent induction of heme oxygenase-1 by resveratrol in human aortic smooth muscle cells, Biochem. Pharmacol., 69, 41, 10.1016/j.bcp.2004.09.015

Olas, 2001, The effect of resveratrol on the platelet secretory process induced by endotoxin and thrombin, Microbios, 105, 7

Orsini, 1997, Isolation, synthesis, and antiplatelet aggregation activity of resveratrol 3-O-beta-d-glucopyranoside and related compounds, J. Nat. Prod., 60, 1082, 10.1021/np970069t

Fremont, 2000, Biological effects of resveratrol, Life Sci., 66, 663, 10.1016/S0024-3205(99)00410-5

Subbaramaiah, 1998, Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells, J. Biol. Chem., 273, 21875, 10.1074/jbc.273.34.21875

Hattori, 2002, Pharmacological preconditioning with resveratrol: role of nitric oxide, Am. J. Physiol. Heart Circ. Physiol., 282, H1988, 10.1152/ajpheart.01012.2001

Hung, 2000, Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes, Cardiovasc. Res., 47, 549, 10.1016/S0008-6363(00)00102-4

Ciolino, 1999, Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP1A1 expression by resveratrol, Mol. Pharmacol., 56, 760

Basly, 2005, Dietary phytoestrogens: potential selective estrogen enzyme modulators?, Planta Med., 71, 287, 10.1055/s-2005-864092

Cos, 2003, Phytoestrogens: recent developments, Planta Med., 69, 589, 10.1055/s-2003-41122

Matthews, 2006, Estrogen receptor and aryl hydrocarbon receptor signaling pathways, Nucl. Recept. Signal, 4, e016, 10.1621/nrs.04016

Rahman, 2004, Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-kappaB and pro-inflammatory gene expression, Biochem. Pharmacol., 68, 1255, 10.1016/j.bcp.2004.05.042

Rahman, 2006, Regulation of inflammation and redox signaling by dietary polyphenols, Biochem. Pharmacol., 72, 1439, 10.1016/j.bcp.2006.07.004

Kundu, 2004, Molecular basis of chemoprevention by resveratrol: NF-kappaB and AP-1 as potential targets, Mutat. Res., 555, 65, 10.1016/j.mrfmmm.2004.05.019

Chun, 2004, Signal transduction pathways regulating cyclooxygenase-2 expression: potential molecular targets for chemoprevention, Biochem. Pharmacol., 68, 1089, 10.1016/j.bcp.2004.05.031

Klinge, 2005, Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells, J. Biol. Chem., 280, 7460, 10.1074/jbc.M411565200

Kotha, 2006, Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein, Mol. Cancer Ther., 5, 621, 10.1158/1535-7163.MCT-05-0268

Lin, 2003, Inhibition of vascular endothelial growth factor-induced angiogenesis by resveratrol through interruption of Src-dependent vascular endothelial cadherin tyrosine phosphorylation, Mol. Pharmacol., 64, 1029, 10.1124/mol.64.5.1029

Storz, 2004, Activation loop phosphorylation controls protein kinase D-dependent activation of nuclear factor kappaB, Mol. Pharmacol., 66, 870, 10.1124/mol.104.000687

Huang, 1999, Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway, Carcinogenesis, 20, 237, 10.1093/carcin/20.2.237

Hsieh, 1999, Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21(WAF1/CIP1), and suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2, Cancer Res., 59, 2596

Hsieh, 1999, Cell cycle effects and control of gene expression by resveratrol in human breast carcinoma cell lines with different metastatic potentials, Int. J. Oncol., 15, 245

She, 2001, Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase, Cancer Res., 61, 1604

Soleas, 2001, Do wine polyphenols modulate p53 gene expression in human cancer cell lines?, Clin. Biochem., 34, 415, 10.1016/S0009-9120(01)00246-6

Shih, 2002, Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK- and p53-dependent mechanism, J. Clin. Endocrinol. Metab., 87, 1223, 10.1210/jcem.87.3.8345

She, 2002, Involvement of c-jun NH(2)-terminal kinases in resveratrol-induced activation of p53 and apoptosis, Mol. Carcinog., 33, 244, 10.1002/mc.10041

Lin, 2002, Resveratrol induced serine phosphorylation of p53 causes apoptosis in a mutant p53 prostate cancer cell line, J. Urol., 168, 748, 10.1016/S0022-5347(05)64739-8

Kuo, 2002, Resveratrol-induced apoptosis is mediated by p53-dependent pathway in Hep G2 cells, Life Sci., 72, 23, 10.1016/S0024-3205(02)02177-X

Alkhalaf, 2007, Resveratrol-induced apoptosis is associated with activation of p53 and inhibition of protein translation in T47D human breast cancer cells, Pharmacology, 80, 134, 10.1159/000103253

Narayanan, 2006, Chemopreventive agents alters global gene expression pattern: predicting their mode of action and targets, Curr. Cancer Drug Targets, 6, 711, 10.2174/156800906779010218

Narayanan, 2003, Differential expression of genes induced by resveratrol in LNCaP cells: P53-mediated molecular targets, Int. J. Cancer, 104, 204, 10.1002/ijc.10932

Narayanan, 2002, Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants, Life Sci., 70, 1821, 10.1016/S0024-3205(02)01481-9

Fulda, 2004, Sensitization for tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by the chemopreventive agent resveratrol, Cancer Res., 64, 337, 10.1158/0008-5472.CAN-03-1656

Holmes-McNary, 2000, Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase, Cancer Res., 60, 3477

Yu, 2001, Resveratrol inhibits phorbol ester and UV-induced activator protein 1 activation by interfering with mitogen-activated protein kinase pathways, Mol. Pharmacol., 60, 217, 10.1124/mol.60.1.217

Jang, 1998, Effects of resveratrol on 12-O-tetradecanoylphorbol-13-acetate-induced oxidative events and gene expression in mouse skin, Cancer Lett., 134, 81, 10.1016/S0304-3835(98)00250-X

Della Ragione, 2002, Antioxidants induce different phenotypes by a distinct modulation of signal transduction, FEBS Lett., 532, 289, 10.1016/S0014-5793(02)03683-9

Quinones, 2003, The egr-1 gene is induced by DNA-damaging agents and non-genotoxic drugs in both normal and neoplastic human cells, Life Sci., 72, 2975, 10.1016/S0024-3205(03)00230-3

Ragione, 2003, p21Cip1 gene expression is modulated by Egr1: a novel regulatory mechanism involved in the resveratrol antiproliferative effect, J. Biol. Chem., 278, 23360, 10.1074/jbc.M300771200

Ahmad, 2001, Resveratrol causes WAF-1/p21-mediated G(1)-phase arrest of cell cycle and induction of apoptosis in human epidermoid carcinoma A431 cells, Clin. Cancer Res., 7, 1466

Mouria, 2002, Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis, Int. J. Cancer, 98, 761, 10.1002/ijc.10202

Tinhofer, 2001, Resveratrol, a tumor-suppressive compound from grapes, induces apoptosis via a novel mitochondrial pathway controlled by Bcl-2, FASEB J., 15, 1613, 10.1096/fj.00-0675fje

Linke, 1996, A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage, Genes Dev., 10, 934, 10.1101/gad.10.8.934

Khan, 2000, Differential requirement for p19ARF in the p53-dependent arrest induced by DNA damage, microtubule disruption, and ribonucleotide depletion, Proc. Natl. Acad. Sci. U.S.A., 97, 3266, 10.1073/pnas.97.7.3266

Bourdon, 2007, Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion, Nat. Genet., 39, 776, 10.1038/ng2040

Tanaka, 2000, A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage, Nature, 404, 42, 10.1038/35003506

Altieri, 2004, Molecular circuits of apoptosis regulation and cell division control: the survivin paradigm, J. Cell. Biochem., 92, 656, 10.1002/jcb.20140

Altieri, 2006, The case for survivin as a regulator of microtubule dynamics and cell-death decisions, Curr. Opin. Cell. Biol., 18, 609, 10.1016/j.ceb.2006.08.015

Fulda, 2004, Sensitization for anticancer drug-induced apoptosis by the chemopreventive agent resveratrol, Oncogene, 23, 6702, 10.1038/sj.onc.1207630

Fulda, 2005, Resveratrol-mediated sensitisation to TRAIL-induced apoptosis depends on death receptor and mitochondrial signalling, Eur. J. Cancer, 41, 786, 10.1016/j.ejca.2004.12.020

Delmas, 2003, Resveratrol-induced apoptosis is associated with Fas redistribution in the rafts and the formation of a death-inducing signaling complex in colon cancer cells, J. Biol. Chem., 278, 41482, 10.1074/jbc.M304896200

Delmas, 2004, Redistribution of CD95, DR4 and DR5 in rafts accounts for the synergistic toxicity of resveratrol and death receptor ligands in colon carcinoma cells, Oncogene, 23, 8979, 10.1038/sj.onc.1208086

Green, 2004, The pathophysiology of mitochondrial cell death, Science, 305, 626, 10.1126/science.1099320

Dorrie, 2001, Resveratrol induces extensive apoptosis by depolarizing mitochondrial membranes and activating caspase-9 in acute lymphoblastic leukemia cells, Cancer Res., 61, 4731

Sareen, 2006, Mitochondria as the primary target of resveratrol-induced apoptosis in human retinoblastoma cells, Invest. Ophthalmol. Vis. Sci., 47, 3708, 10.1167/iovs.06-0119

Jiang, 2005, Resveratrol-induced apoptotic death in human U251 glioma cells, Mol. Cancer Ther., 4, 554, 10.1158/1535-7163.MCT-04-0056

Mohan, 2006, Caspase-2 triggers Bax-Bak-dependent and -independent cell death in colon cancer cells treated with resveratrol, J. Biol. Chem., 281, 17599, 10.1074/jbc.M602641200

Moll, 2005, Transcription-independent pro-apoptotic functions of p53, Curr. Opin. Cell. Biol., 17, 631, 10.1016/j.ceb.2005.09.007

Lassus, 2002, Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization, Science, 297, 1352, 10.1126/science.1074721

Bader, 2005, Oncogenic PI3K deregulates transcription and translation, Nat. Rev. Cancer, 5, 921, 10.1038/nrc1753

Vivanco, 2002, The phosphatidylinositol 3-Kinase AKT pathway in human cancer, Nat. Rev. Cancer, 2, 489, 10.1038/nrc839

Sexton, 2006, Resveratrol interferes with AKT activity and triggers apoptosis in human uterine cancer cells, Mol. Cancer, 5, 45, 10.1186/1476-4598-5-45

Aziz, 2006, Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3’-kinase/Akt pathway and Bcl-2 family proteins, Mol. Cancer Ther., 5, 1335, 10.1158/1535-7163.MCT-05-0526

Bhardwaj, 2007, Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-{kappa}B-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells, Blood, 109, 2293, 10.1182/blood-2006-02-003988

Li, 2006, Resveratrol-induced cell inhibition of growth and apoptosis in MCF7 human breast cancer cells are associated with modulation of phosphorylated Akt and caspase-9, Appl. Biochem. Biotechnol., 135, 181, 10.1385/ABAB:135:3:181

Haider, 2002, Resveratrol suppresses angiotensin II-induced Akt/protein kinase B and p70 S6 kinase phosphorylation and subsequent hypertrophy in rat aortic smooth muscle cells, Mol. Pharmacol., 62, 772, 10.1124/mol.62.4.772

Cao, 2004, trans-3,4,5′-Trihydroxystibene inhibits hypoxia-inducible factor 1alpha and vascular endothelial growth factor expression in human ovarian cancer cells, Clin. Cancer Res., 10, 5253, 10.1158/1078-0432.CCR-03-0588

Zhang, 2005, Resveratrol inhibits hypoxia-induced accumulation of hypoxia-inducible factor-1alpha and VEGF expression in human tongue squamous cell carcinoma and hepatoma cells, Mol. Cancer Ther., 4, 1465, 10.1158/1535-7163.MCT-05-0198

Pozo-Guisado, 2004, Resveratrol modulates the phosphoinositide 3-kinase pathway through an estrogen receptor alpha-dependent mechanism: relevance in cell proliferation, Int. J. Cancer, 109, 167, 10.1002/ijc.11720

Brownson, 2002, Flavonoid effects relevant to cancer, J. Nutr., 132, 3482S, 10.1093/jn/132.11.3482S

Zamin, 2006, Protective effect of resveratrol against oxygen-glucose deprivation in organotypic hippocampal slice cultures: involvement of PI3-K pathway, Neurobiol. Dis., 24, 170, 10.1016/j.nbd.2006.06.002

Dolfini, 2007, Resveratrol impairs the formation of MDA-MB-231 multicellular tumor spheroids concomitant with ceramide accumulation, Cancer Lett., 249, 143, 10.1016/j.canlet.2006.08.013

Sala, 2003, Resveratrol structure and ceramide-associated growth inhibition in prostate cancer cells, Drugs Exp. Clin. Res., 29, 263

Scarlatti, 2007, Resveratrol sensitization of DU145 prostate cancer cells to ionizing radiation is associated to ceramide increase, Cancer Lett., 253, 124, 10.1016/j.canlet.2007.01.014

Scarlatti, 2003, Resveratrol induces growth inhibition and apoptosis in metastatic breast cancer cells via de novo ceramide signaling, FASEB J., 17, 2339, 10.1096/fj.03-0292fje

Ingram, 2006, Calorie restriction mimetics: an emerging research field, Aging Cell., 5, 97, 10.1111/j.1474-9726.2006.00202.x

Howitz, 2003, Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan, Nature, 425, 191, 10.1038/nature01960

Kobayashi, 2005, SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress, Int. J. Mol. Med., 16, 237

Lagouge, 2006, Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha, Cell, 127, 1109, 10.1016/j.cell.2006.11.013

Baur, 2006, Resveratrol improves health and survival of mice on a high-calorie diet, Nature, 444, 337, 10.1038/nature05354

Kim, 2007, SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis, EMBO J, 26, 3169, 10.1038/sj.emboj.7601758

Sinclair, 2005, Sirtuins for healthy neurons, Nat. Genet., 37, 339, 10.1038/ng0405-339

Parker, 2005, Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons, Nat. Genet., 37, 349, 10.1038/ng1534

Anekonda, 2006, Neuronal protection by sirtuins in Alzheimer's disease, J. Neurochem., 96, 305, 10.1111/j.1471-4159.2005.03492.x

Marambaud, 2005, Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides, J. Biol. Chem., 280, 37377, 10.1074/jbc.M508246200

Walle, 2004, High absorption but very low bioavailability of oral resveratrol in humans, Drug Metab. Dispos., 32, 1377, 10.1124/dmd.104.000885

Karlsson, 2000, trans-resveratrol protects embryonic mesencephalic cells from tert-butyl hydroperoxide: electron paramagnetic resonance spin trapping evidence for a radical scavenging mechanism, J. Neurochem., 75, 141, 10.1046/j.1471-4159.2000.0750141.x

Asensi, 2002, Inhibition of cancer growth by resveratrol is related to its low bioavailability, Free Radic. Biol. Med., 33, 387, 10.1016/S0891-5849(02)00911-5

Marier, 2002, Metabolism and disposition of resveratrol in rats: extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model, J. Pharmacol. Exp. Ther., 302, 369, 10.1124/jpet.102.033340

Yu, 2003, Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate, Rapid Commun. Mass Spectrom., 17, 307, 10.1002/rcm.918

Goldberg, 2003, Absorption of three wine-related polyphenols in three different matrices by healthy subjects, Clin. Biochem., 36, 79, 10.1016/S0009-9120(02)00397-1

Meng, 2004, Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice, J. Agric. Food Chem., 52, 935, 10.1021/jf030582e

Wang, 2002, An LC–MS method for analyzing total resveratrol in grape juice, cranberry juice, and in wine, J. Agric. Food Chem., 50, 431, 10.1021/jf010812u

Miksits, 2005, Sulfation of resveratrol in human liver: evidence of a major role for the sulfotransferases SULT1A1 and SULT1E1, Xenobiotica, 35, 1101, 10.1080/00498250500354253

Maier-Salamon, 2006, Increased transport of resveratrol across monolayers of the human intestinal Caco-2 cells is mediated by inhibition and saturation of metabolites, Pharm. Res., 23, 2107, 10.1007/s11095-006-9060-z

Potter, 2002, The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1, Br. J. Cancer, 86, 774, 10.1038/sj.bjc.6600197

Wolter, 2002, Piceatannol, a natural analog of resveratrol, inhibits progression through the S phase of the cell cycle in colorectal cancer cell lines, J. Nutr., 132, 298, 10.1093/jn/132.2.298

Cai, 2004, The 3,4-dihydroxyl groups are important for trans-resveratrol analogs to exhibit enhanced antioxidant and apoptotic activities, Anticancer Res., 24, 999

Hung, 2001, Beneficial effects of astringinin, a resveratrol analogue, on the ischemia and reperfusion damage in rat heart, Free Radic. Biol. Med., 30, 877, 10.1016/S0891-5849(01)00474-9

Hung, 2002, The protective effect of resveratrols on ischaemia-reperfusion injuries of rat hearts is correlated with antioxidant efficacy, Br. J. Pharmacol., 135, 1627, 10.1038/sj.bjp.0704637

Murias, 2005, Antioxidant, prooxidant and cytotoxic activity of hydroxylated resveratrol analogues: structure–activity relationship, Biochem. Pharmacol., 69, 903, 10.1016/j.bcp.2004.12.001

Gandhi, 1994, Modulation of arabinosylcytosine metabolism during leukemia therapy, Adv. Exp. Med. Biol., 370, 119, 10.1007/978-1-4615-2584-4_27

Robinson, 2003, Enhanced radiosensitization with gemcitabine in mismatch repair-deficient HCT116 cells, Cancer Res., 63, 6935

Horvath, 2006, Cytotoxic and biochemical effects of 3,3’,4,4’,5,5’-hexahydroxystilbene, a novel resveratrol analog in HL-60 human promyelocytic leukemia cells, Exp. Hematol., 34, 1377, 10.1016/j.exphem.2006.05.018

Roberti, 2003, Synthesis and biological evaluation of resveratrol and analogues as apoptosis-inducing agents, J. Med. Chem., 46, 3546, 10.1021/jm030785u

Tolomeo, 2005, Pterostilbene and 3′-hydroxypterostilbene are effective apoptosis-inducing agents in MDR and BCR-ABL-expressing leukemia cells, Int. J. Biochem. Cell. Biol., 37, 1709, 10.1016/j.biocel.2005.03.004

Murias, 2004, Resveratrol analogues as selective cyclooxygenase-2 inhibitors: synthesis and structure–activity relationship, Bioorg. Med. Chem., 12, 5571, 10.1016/j.bmc.2004.08.008

Basly, 2000, Estrogenic/antiestrogenic and scavenging properties of (E)- and (Z)-resveratrol, Life Sci., 66, 769, 10.1016/S0024-3205(99)00650-5

Chang, 2000, Trans-resveratrol modulates the catalytic activity and mRNA expression of the procarcinogen-activating human cytochrome P450 1B1, Can. J. Physiol. Pharmacol., 78, 874, 10.1139/y00-067

Chang, 2001, Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism-based inactivation of CYP1A2, J. Pharmacol. Exp. Ther., 299, 874

Manna, 2000, Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation, J. Immunol., 164, 6509, 10.4049/jimmunol.164.12.6509

Chen, 2004, Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells, Carcinogenesis, 25, 2005, 10.1093/carcin/bgh183

Clement, 1998, Chemopreventive agent resveratrol, a natural product derived from grapes, triggers CD95 signaling-dependent apoptosis in human tumor cells, Blood, 92, 996, 10.1182/blood.V92.3.996

Chan, 2000, Resveratrol, a red wine constituent, is a mechanism-based inactivator of cytochrome P450 3A4, Life Sci., 67, 3103, 10.1016/S0024-3205(00)00888-2

Martinez, 2000, Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production, Biochem. Pharmacol., 59, 865, 10.1016/S0006-2952(99)00380-9

Atten, 2001, Resveratrol-induced inactivation of human gastric adenocarcinoma cells through a protein kinase C-mediated mechanism, Biochem. Pharmacol., 62, 1423, 10.1016/S0006-2952(01)00788-2

Mahyar-Roemer, 2001, Resveratrol induces colon tumor cell apoptosis independently of p53 and precede by epithelial differentiation, mitochondrial proliferation and membrane potential collapse, Int. J. Cancer, 94, 615, 10.1002/ijc.1516

Haworth, 2001, Inhibition of protein kinase D by resveratrol, Biochem. Pharmacol., 62, 1647, 10.1016/S0006-2952(01)00807-3

Wu, 2004, Effect of resveratrol and in combination with 5-FU on murine liver cancer, World J. Gastroenterol., 10, 3048, 10.3748/wjg.v10.i20.3048

Banerjee, 2002, Suppression of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in rats by resveratrol: role of nuclear factor-kappaB, cyclooxygenase 2, and matrix metalloprotease 9, Cancer Res., 62, 4945

Miura, 2003, Hypolipidemic action of dietary resveratrol, a phytoalexin in grapes and red wine, in hepatoma-bearing rats, Life Sci., 73, 1393, 10.1016/S0024-3205(03)00469-7

Tessitore, 2000, Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21(CIP) expression, Carcinogenesis, 21, 1619, 10.1093/carcin/21.5.619

Schneider, 2001, Resveratrol inhibits intestinal tumorigenesis and modulates host-defense-related gene expression in an animal model of human familial adenomatous polyposis, Nutr. Cancer, 39, 102, 10.1207/S15327914nc391_14

Provinciali, 2005, Effect of resveratrol on the development of spontaneous mammary tumors in HER-2/neu transgenic mice, Int. J. Cancer, 115, 36, 10.1002/ijc.20874

Garvin, 2006, Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo, Cancer Lett., 231, 113, 10.1016/j.canlet.2005.01.031

Chen, 2004, Resveratrol-induced cellular apoptosis and cell cycle arrest in neuroblastoma cells and antitumor effects on neuroblastoma in mice, Surgery, 136, 57, 10.1016/j.surg.2004.01.017

Tseng, 2004, Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats, Clin. Cancer Res., 10, 2190, 10.1158/1078-0432.CCR-03-0105

Kimura, 2001, Resveratrol isolated from Polygonum cuspidatum root prevents tumor growth and metastasis to lung and tumor-induced neovascularization in Lewis lung carcinoma-bearing mice, J. Nutr., 131, 1844, 10.1093/jn/131.6.1844

Caltagirone, 2000, Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential, Int. J. Cancer, 87, 595, 10.1002/1097-0215(20000815)87:4<595::AID-IJC21>3.0.CO;2-5

Carbo, 1999, Resveratrol, a natural product present in wine, decreases tumour growth in a rat tumour model, Biochem. Biophys. Res. Commun., 254, 739, 10.1006/bbrc.1998.9916

Li, 2002, Suppression of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in F344 rats by resveratrol, Carcinogenesis, 23, 1531, 10.1093/carcin/23.9.1531

Sengottuvelan, 2006, Chemopreventive effect of trans-resveratrol—a phytoalexin against colonic aberrant crypt foci and cell proliferation in 1,2-dimethylhydrazine induced colon carcinogenesis, Carcinogenesis, 27, 1038, 10.1093/carcin/bgi286

Brakenhielm, 2001, Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes, FASEB J., 15, 1798, 10.1096/fj.01-0028fje

Zhou, 2005, Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice, World J. Gastroenterol., 11, 280, 10.3748/wjg.v11.i2.280

Reagan-Shaw, 2004, Modulations of critical cell cycle regulatory events during chemoprevention of ultraviolet B-mediated responses by resveratrol in SKH-1 hairless mouse skin, Oncogene, 23, 5151, 10.1038/sj.onc.1207666

Aziz, 2005, Chemoprevention of skin cancer by grape constituent resveratrol: relevance to human disease?, FASEB J., 19, 1193, 10.1096/fj.04-3582fje

Afaq, 2003, Prevention of short-term ultraviolet B radiation-mediated damages by resveratrol in SKH-1 hairless mice, Toxicol. Appl. Pharmacol., 186, 28, 10.1016/S0041-008X(02)00014-5