Resveratrol: From basic studies to bedside

Cancer Treatment and Research

Volumn 159, Issue , 2014, Pages 167-184

  Borriello, Adriana ^a   Bencivenga, Debora ^a   Caldarelli, Ilaria ^a   Tramontano, Annunziata ^a   Borgia, Alessia ^a   Zappia, Vincenzo ^a   Ragione, Fulvio Della ^a  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

Author keywords

AMPK; Cancer therapy; PGC 1 ; Resveratrol; Sirtuin

Indexed keywords

BORTEZOMIB; CYCLIC AMP; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; MITOCHONDRIAL TRANSCRIPTION FACTOR A; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PHOSPHODIESTERASE; PLACEBO; RESVERATROL; SIRTUIN 1; TRANSCRIPTION FACTOR NRF1; TRANSCRIPTION FACTOR NRF2; ANTINEOPLASTIC AGENT; STILBENE DERIVATIVE;

ANTIANGIOGENIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; BREAST CANCER; COLON CARCINOMA; COLORECTAL CANCER; DIARRHEA; DIGESTIVE SYSTEM CANCER; DOSE RESPONSE; DRUG ACCUMULATION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG METABOLISM; DRUG POTENCY; DRUG STRUCTURE; DRUG TARGETING; DRUG TOLERABILITY; ENERGY METABOLISM; ESOPHAGUS CANCER; FIBROSARCOMA; FOLLICULAR LYMPHOMA; HEADACHE; HUMAN; LEUKEMIA; LIVER CELL CARCINOMA; LOOSE FECES; MAXIMUM PLASMA CONCENTRATION; MULTIPLE MYELOMA; NEUROBLASTOMA; NONHUMAN; PANCREAS CANCER; PLEIOTROPY; PRIORITY JOURNAL; PROSTATE CANCER; RASH; SINGLE DRUG DOSE; SKIN CANCER; STOMACH CANCER; UNSPECIFIED SIDE EFFECT; ANIMAL; CELL AGING; CLINICAL TRIAL (TOPIC); DRUG EFFECTS; MEDICAL RESEARCH; NEOPLASMS;

ANIMALS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; BIOMEDICAL RESEARCH; CELL AGING; CLINICAL TRIALS AS TOPIC; HUMANS; NEOPLASMS; STILBENES;

EID: 84897234415     PISSN: 09273042     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-3-642-38007-5_10     Document Type: Article

References (110)

1. Ahmad KA, Clement MV, Hanif IM et al (2004) Resveratrol inhibits drug-induced apoptosis in human leukemia cells by creating an intracellular milieu nonpermissive for death execution. Cancer Res 64:1452–1459
2. Alex D, Leong EC, Zhang ZJ et al (2010) Resveratrol derivative, trans-3, 5, 49-trimethoxystilbene, exerts antiangiogenic and vascular disrupting effects in zebrafish through the downregulation of VEGFR2 and cell cycle modulation. J Cell Biochem 109:339–346
3. Alkhalaf M, El-Mowafy A, Renno W et al (2008) Resveratrol-induced apoptosis in human breast cancer cells is mediated primarily through the caspase-3-dependent pathway. Arch Med Res 39:162–168
4. Almeida L, Vaz-da-Silva M, Falcao A et al (2009) Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers. Mol Nutr Food Res 53:7–15
5. Asou H, Koshizuka K, Kyo T et al (2002) Resveratrol a natural product derived from grapes, is a new inducer of differentiation in human myeloid leukemias. Int J Hematol 75:528–533
6. Aziz MH, Afaq F, Ahmad N (2005) Prevention of ultraviolet-B radiation damage by resveratrol in mouse skin is mediated via modulation in survivin. Photochem Photobiol 81:25–31
7. Aziz MH, Nihal M, Fu VX et al (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 5:1335–1341
8. Banerjee Mustafi S, Chakraborty PK, Raha S (2010) Modulation of Akt and ERK1/2 pathways by resveratrol in chronic myelogenous leukemia (CML) cells results in the downregulation of Hsp70. PLoS ONE 5:e8719
9. Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5:493–506
10. Baur JA, Pearson KJ, Price NL et al (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342
11. Beher D, Wu J, Cumine S et al (2009) Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem Biol Drug Des 74:619–624
12. Bhardwaj A, Sethi G, Vadhan-Raj S et al (2004) Isorhapontigenin and resveratrol suppress oxLDL-induced proliferation and activation of ERK1/2 mitogen-activated protein kinases of bovine aortic smooth muscle cells. Biochem Pharmacol 67:777–785
13. Bhardwaj A, Sethi G, Vadhan-Raj S et al (2007) Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB regulated antiapoptotic and cell survival gene products in human multiple myeloma cells. Blood 109:2293–2302
14. Boissy P, Andersen TL, Abdallah BM et al (2005) Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoblast differentiation. Cancer Res 65:9943–9952
15. Boocock DJ, Faust GE, Patel KR (2007) Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Canc Epidemiol Biomarkers Prev 16:1246–1252
16. Bråkenhielm E, Cao R, Cao Y (2001) Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes. FASEB J 15:1798–1800
17. Brown VA, Patel KR, Viskaduraki M et al (2010) Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res 70:9003–9011
18. Calabrese EJ, Mattson MP, Calabrese V (2010) Resveratrol commonly displays hormesis: occurrence and biomedical significance. Hum Exp Toxicol 29:980–1015
19. Cao Y, Fu ZD, Wang F et al (2005) Anti-angiogenic activity of resveratrol, a natural compound from medicinal plants. J Asian Nat Prod Res 7:205–213
20. Cao Z, Fang J, Xia C et al (2004) trans-3, 4, 5’-Trihydroxystilbene inhibits hypoxia-inducible factor 1alpha and vascular endothelial growth factor expression in human ovarian cancer cells. Clin Cancer Res 10:5253–5263
21. Chan JY, Phoo MS, Clement MV et al (2008) Resveratrol displays converse dose-related effects on 5-fluorouracil-evoked colon cancer cell apoptosis: the roles of caspase-6 and p53. Cancer Biol Ther 7:1305–1312
22. Chan WK, Delucchi AB (2000) Resveratrol, a red wine constituent, is a mechanism-based inactivator of cytochrome P450 3A4. Life Sci 67:3103–3012
23. Chen Q, Ganapathy S, Singh KP et al (2010) Resveratrol induces growth arrest and apoptosis through activation of FOXO transcription factors in prostate cancer cells. PLoS ONE 5:e15288
24. Chen ZH, Hurh YJ, Na HK et al (2004) Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells. Carcinogenesis 25:2005–2013
25. Ciolino HP, Daschner PJ, Yeh GC (1998) Resveratrol inhibits transcription of CYP1A1 in vitro by preventing activation of the aryl hydrocarbon receptor. Cancer Res 58:5707–5712
26. Clément MV, Hirpara JL, Chawdhury SH et al (1998) Chemopreventive agent resveratrol, a natural product derived from grapes, triggers CD95 signaling-dependent apoptosis in human tumor cells. Blood 92:996–1002
27. Cucciolla V, Borriello A, Oliva A et al (2007) Resveratrol: from basic science to the clinic. Cell Cycle 6:2495–2510
28. Dai H, Kustigian L, Carney D et al (2010) SIRT1 activation by small molecules: kinetic and biophysical evidence for direct interaction of enzyme and activator. J Biol Chem 285:32695–32703
29. Della Ragione F, Cucciolla V, Borriello A et al (1998) Resveratrol arrests the cell division cycle at S/G2 phase transition. Biochem Biophys Res Commun 250:53–58
30. Della Ragione F, Cucciolla V, Criniti V et al (2003) p21Cip1 gene expression is modulated by Egr1: a novel regulatory mechanism involved in the resveratrol antiproliferative effect. J Biol Chem 278:23360–23368
31. El-Mowafy AM, White RE (1999) Resveratrol inhibits MAPK activity and nuclear translocation in coronary artery smooth muscle: reversal of endothelin-1 stimulatory effects. FEBS Lett 451:63–67
32. Elliott PJ, Walpole S, Morelli L et al (2009) Resveratrol/SRT501. Sirtuin SIRT1 activator, Treatment of type 2 diabetes. Drugs Fut 34:291–295
33. Estrov Z, Shishodia S, Faderl S et al (2003) Resveratrol blocks interleukin-1beta-induced activation of the nuclear transcription factor NF-kappaB, inhibits proliferation, causes Sphase arrest, and induces apoptosis of acute myeloid leukemia cells. Blood 102:987–995
34. Floreani M, Napoli E, Quintieri L et al (2003) Oral administration of trans-resveratrol to guinea pigs increases cardiac DT-diaphorase and catalase activities, and protects isolated atria from menadione toxicity. Life Sci 72:2741–2750
35. Fulda S, Debatin KM (2005) Resveratrol-mediated sensitisation to TRAIL-induced apoptosis depends on death receptor and mitochondrial signalling. Eur J Cancer 41:786–798
36. George J, Singh M, Srivastava AK et al (2011) Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53. PLoS ONE 6:e23395
37. Guarente L (1999) Diverse and dynamic functions of the Sir silencing complex. Nat Genet 23:281–285
38. Haider UG, Roos TU, Kontaridis MI et al (2005) Resveratrol inhibits angiotensin II-and epidermal growth factor-mediated Akt activation: role of Gab1 and Shp2. Mol Pharmacol 68:41–48
39. Haider UG, Sorescu D, Griendling KK et al (2002) Resveratrol suppresses angiotensin IIinduced Akt/protein kinase B and p70 S6 kinase phosphorylation and subsequent hypertrophy in rat aortic smooth muscle cells. Mol Pharmacol 62:772–777
40. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674
41. Hayashibara T, Yamada Y, Nakayama S et al (2002) Resveratrol induces downregulation in survivin expression and apoptosis in HTLV-1-infected cell lines: a prospective agent for adult T cell leukemia chemotherapy. Nutr Cancer 44:193–201
42. Holmes-McNary M, Baldwin AS Jr (2000) Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase. Cancer Res 60:3477–3483
43. Howells LM, Berry DP, Elliott PJ et al (2011) Phase I randomised double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases—safety, pharmacokinetics and pharmacodynamics. Cancer Prev Res (Phila) 4:1419–1425
44. Howitz KT, Bitterman KJ, Cohen HY et al (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191–196
45. Jang M, Cai L, Udeani GO et al (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275:218–222
46. Kaminski J, Lançon A, Aires V et al (2012) Resveratrol initiates differentiation of mouse skeletal muscle-derived C2C12 myoblasts. Biochem Pharmacol pii S0006–2952(12):00579–5. doi:10.1016/j.bcp.2012.08.023
47. Ko YC, Chang CL, Chien HF et al (2011) Resveratrol enhances the expression of death receptor Fas/CD95 and induces differentiation and apoptosis in anaplastic large-cell lymphoma cells. Cancer Lett 309:46–53
48. Kundu JK, Shin YK, Kim SH et al (2006) Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-kappaB in mouse skin by blocking IkappaB kinase activity. Carcinogenesis 27:1465–1474
49. la Porte C, Voduc N, Zhang G et al (2010) Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects. Clin Pharmacokinet 49:449–454
50. Lagouge M, Argmann C, Gerhart-Hines Z et al (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122
51. Lee JE, Safe S (2001) Involvement of a post-transcriptional mechanism in the inhibition of CYP1A1 expression by resveratrol in breast cancer cells. Biochem Pharmacol 62:1113–1124
52. Lee MH, Choi BY, Kundu JK et al (2009) Resveratrol suppresses growth of human ovarian cancer cells in culture and in a murine xenograft model: eukaryotic elongation factor 1A2 as a potential target. Cancer Res 69:7449–7458
53. Leong CW, Wong CH, Lao SC et al (2007) Effect of resveratrol on proliferation and differentiation of embryonic cardiomyoblasts. Biochem Biophys Res Commun 360:173–180
54. Li F, Gong Q, Dong H et al (2012) Resveratrol, a neuroprotective supplement for Alzheimer’s disease. Curr Pharm Des 18:27–33
55. Lin HY, Tang HY, Keating T et al (2008) Resveratrol is pro-apoptotic and thyroid hormone is anti-apoptotic in glioma cells: both actions are integrin and ERK mediated. Carcinogenesis 29:62–69
56. Mader I, Wabitsch M, Debatin KM et al (2010) Identification of a novel proapoptotic function of resveratrol in fat cells: SIRT1—independent sensitization to TRAIL-induced apoptosis. FASEB J 24:1997–2009
57. Manna SK, Mukhopadhyay A, Aggarwal BB (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 164:6509–6519
58. Michan S, Sinclair D (2007) Sirtuins in mammals: insights into their biological function. Biochem J 404:1–13
59. Miller RA, Harrison DE, Astle CM et al (2011) Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci 66:191–201
60. Mohan J, Gandhi AA, Bhavya BC et al (2006) Caspase-2 triggers Bax-Bak-dependent and-independent cell death in colon cancer cells treated with resveratrol. J Biol Chem 281:17599–17611
61. Morselli E, Mariño G, Bennetzen MV et al (2011) Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome. J Cell Biol 192:615–629
62. Nguyen AV, Martinez M, Stamos MJ et al (2009) Results of a phase I pilot clinical trial examining the effect of plant-derived resveratrol and grape powder on Wnt pathway target gene expression in colonic mucosa and colon cancer. Canc Manag Res 1:25–37
63. Opipari AW Jr, Tan L, Boitano AE et al (2004) Resveratrol-induced autophagocytosis in ovarian cancer cells. Cancer Res 64:696–703
64. Park JW, Choi YJ, Suh SI et al (2001) Bcl-2 overexpression attenuates resveratrol-induced apoptosis in U937 cells by inhibition of caspase-3 activity. Carcinogenesis 22:1633–1639
65. Park SJ, Ahmad F, Philp A et al (2012) Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP Phosphodiesterases. Cell 148:421–433
66. Patel KR, Brown VA, Jones DJ et al (2010) Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Cancer Res 70:7392–7399
67. Pearson KJ, Baur JA, Lewis KN et al (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8:157–168
68. Pöhland T, Wagner S, Mahyar-Roemer M et al (2006) Bax and Bak are the critical complementary effectors of colorectal cancer cell apoptosis by chemopreventive resveratrol. Anticancer Drugs 17:471–478
69. Pozo-Guisado E, Lorenzo-Benayas MJ, Fernández-Salguero PM (2004) Resveratrol modulates the phosphoinositide 3-kinase pathway through an estrogen receptor alphadependent mechanism: relevance in cell proliferation. Int J Cancer 109:167–173
70. Pozo-Guisado E, Merino JM, Mulero-Navarro S et al (2005) Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspase-independent mechanism with downregulation of Bcl-2 and NF-kappaB. Int J Cancer 115:74–84
71. Price NL, Gomes AP, Ling AJ et al (2012) SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab 15:675–690
72. Puissant A, Auberger P (2010) AMPK-and p62/SQSTM1-dependent autophagy mediate Resveratrol-induced cell death in chronic myelogenous leukemia. Autophagy 6:655–657
73. Puissant A, Robert G, Fenouille N et al (2010) Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation. Cancer Res 70:1042–1052
74. Reybier K, Perio P, Ferry G et al (2011) Insights into the redox cycle of human quinine reductase 2. Free Radic Res 45:1184–1195
75. Roy P, Kalra N, Prasad S et al (2009) Chemopreventive potential of resveratrol in mouse skin tumors through regulation of mitochondrial and PI3 K/AKT signaling pathways. Pharm Res 26:211–217
76. Scarlatti F, Maffei R, Beau I et al (2008) Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells. Cell Death Differ 8:1318–1329
77. Shankar S, Chen Q, Siddiqui I et al (2007) Sensitization of TRAIL-resistant LNCaP cells by resveratrol (3, 49, 5 tri-hydroxystilbene): molecular mechanisms and therapeutic potential. J Mol Signal 2:7
78. Shankar S, Siddiqui I, Srivastava RK (2007) Molecular mechanisms of resveratrol (3, 4, 5-trihydroxy-trans-stilbene) and its interaction with TNF-related apoptosis inducing ligand (TRAIL) in androgen-insensitive prostate cancer cells. Mol Cell Biochem 304:273–285
79. She QB, Huang C, Zhang Y et al (2002) Involvement of c-jun NH(2)-terminal kinases in resveratrol-induced activation of p53 and apoptosis. Mol Carcinog 33:244–250
80. Shih A, Zhang S, Cao HJ et al (2004) Inhibitory effect of epidermal growth factor on resveratrol-induced apoptosis in prostate cancer cells is mediated by protein kinase C-alpha. Mol Cancer Ther 3:1355–1364
81. Smith TG, Robbins PA, Ratcliffe PJ (2008) The human side of hypoxia-inducible factor. Br J Haematol 141:325–334
82. Soleas GJ, Yan J, Goldberg DM (2001) Measurement of trans-resveratrol, (1)-catechin, and quercetin in rat and human blood and urine by gas chromatography with mass selective detection. Methods Enzymol 335:130–145
83. Soleas GJ, Yan J, Goldberg DM (2001) Ultrasensitive assay for three polyphenols (catechin, quercetin and resveratrol) and their conjugates in biological fluids utilizing gas chromatography with mass selective detection. J Chromatogr B Biomed Sci Appl 757:161–172
84. Spanier G, Xu H, Xia N et al (2009) Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4). J Physiol Pharmacol 60:111–116
85. Srivastava RK, Unterman TG, Shankar S (2010) FOXO transcription factors and VEGF neutralizing antibody enhance antiangiogenic effects of resveratrol. Mol Cell Biochem 337:201–212
86. Stewart JR, Christman KL, O’Brian CA (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 60:1355–1359
87. Subbaramaiah K, Chung WJ, Michaluart P et al (1998) Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J Biol Chem 273:21875–21882
88. Szewczuk LM, Forti L, Stivala LA et al (2004) Resveratrol is a peroxidase-mediated inactivator of COX-1 but not COX-2: a mechanistic approach to the design of COX-1 selective agents. J Biol Chem 279:22727–22737
89. Takaoka M (1939) Resveratrol, a new phenolic compound, from Veratrum grandiflorum. Nippon Kagaku Kaishi 60:1090–1100
90. Tang HY, Shih A, Cao HJ et al (2006) Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells. Mol Cancer Ther 5:2034–2042
91. Timmers S, Konings E, Bilet L et al (2011) Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab 14:612–622
92. Tinhofer I, Bernhard D, Senfter M et al (2001) Resveratrol, a tumor-suppressive compound from grapes, induces apoptosis via a novel mitochondrial pathway controlled by Bcl-2. FASEB J 15:1613–1615
93. Tomé-Carneiro J, Gonzálvez M, Larrosa M et al (2012) One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. Am J Cardiol 110:356–363
94. Trincheri NF, Nicotra G, Follo C et al (2007) Resveratrol induces cell death in colorectal cancer cells by a novel pathway involving lysosomal cathepsin D. Carcinogenesis 28:922–931
95. Ulrich S, Huwiler A, Loitsch S et al (2007) De novo ceramide biosynthesis is associated with resveratrol-induced inhibition of ornithine decarboxylase activity. Biochem Pharmacol 74:281–289
96. Vang O, Ahmad N, Baile CA et al (2011) What is new for an old molecule? Systematic review and recommendations on the use of resveratrol. PLoS ONE 6:e19881
97. Walle T, Hsieh F, DeLegge MH et al (2004) High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 32:1377–1382
98. Wang Y, Romigh T, He X et al (2010) Resveratrol regulates the PTEN/AKT pathway through androgen receptor dependent and-independent mechanisms in prostate cancer cell lines. Hum Mol Genet 19:4319–4329
99. Wong RH, Howe PR, Buckley JD et al (2011) Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr Metab Cardiovasc Dis 21:851–856
100. Woo JH, Lim JH, Kim YH et al (2004) Resveratrol inhibits phorbol myristate acetateinduced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transduction. Oncogene 23:1845–1853
101. Wu H, Liang X, Fang Y et al (2008) Resveratrol inhibits hypoxia-induced metastasis potential enhancement by restricting hypoxia-induced factor-1 alpha expression in colon carcinoma cells. Biomed Pharmacother 62:613–621
102. Wu Y, Li X, Zhu JX et al (2011) Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson’s disease. Neurosignals 19:163–174
103. Yamamoto H, Schoonjans K, Auwerx J (2007) Sirtuin functions in health and disease. Mol Endocrinol 21:1745–1755
104. Yu LJ, Wu ML, Li H et al (2008) Inhibition of STAT3 expression and signaling in resveratrol-differentiated medulloblastoma cells. Neoplasia 10:736–744
105. Yu R, Hebbar V, Kim DW et al (2001) Resveratrol inhibits phorbol ester and UV-induced activator protein 1 activation by interfering with mitogen-activated protein kinase pathways. Mol Pharmacol 60:217–224
106. Zamora-Ros R, Urpi-Sarda M, Lamuela-Raventós RM et al (2012) High urinary levels of resveratrol metabolites are associated with a reduction in the prevalence of cardiovascular risk factors in high-risk patients. Pharmacol Res 65:615–620
107. Zhang F, Liu J, Shi JS (2010) Anti-inflammatory activities of resveratrol in the brain: role of resveratrol in microglial activation. Eur J Pharmacol 636:1–7
108. Zhang S, Cao HJ, Davis FB et al (2004) Oestrogen inhibits resveratrol-induced posttranslational modification of p53 and apoptosis in breast cancer cells. Br J Cancer 91:178–185
109. Zhao K, Harshaw R, Chai X et al (2004) Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD +-dependent Sir2 histone/protein deacetylases. Proc Natl Acad Sci USA 101:8563–8568
110. Zykova TA, Zhu F, Zhai X et al (2008) Resveratrol directly targets COX-2 to inhibit carcinogenesis. Mol Carcinog 47:797–805