Role of natural stilbenes in the prevention of cancer

Oxidative Medicine and Cellular Longevity

Volumn 2016, Issue , 2016, Pages

  Sirerol, J Antoni ^a   Rodríguez, María L ^a   Mena, Salvador ^a   Asensi, Miguel A ^a   Estrela, José M ^a   Ortega, Angel L ^a  

^a UNIVERSITY OF VALENCIA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMALS; BIOACTIVITY; BIOCHEMISTRY; CELL DEATH; DRUG INTERACTIONS; DRUG PRODUCTS;

ANTI-INFLAMMATORIES; ANTICANCER DRUG; CHEMOPREVENTION; DRUG FORMULATIONS; NATURAL STRUCTURES; PHARMACOLOGICAL ACTIVITY; PHYTOCHEMICALS; TARGET PROTEINS;

DISEASES;

PICEATANNOL; PINOSYLVIN; PTEROSTILBENE; RESVERATROL; STILBENE DERIVATIVE;

CANCER PREVENTION; CHEMOPROPHYLAXIS; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; DRUG MECHANISM; HUMAN; IN VIVO STUDY; NONHUMAN; REVIEW; STRUCTURE ACTIVITY RELATION; ANIMAL; NEOPLASMS;

DISEASES; DRUGS; FLAVONOIDS; PROTEINS; STILBENES;

ANIMALS; CHEMOPREVENTION; CLINICAL TRIALS AS TOPIC; HUMANS; NEOPLASMS; STILBENES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84969995832     PISSN: 19420900     EISSN: 19420994     Source Type: Journal    
DOI: 10.1155/2016/3128951     Document Type: Review

References (175)

1. J. Ferlay, E. Steliarova-Foucher, J. Lortet-Tieulent et al., "Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012," European Journal of Cancer, vol. 49, no. 6, pp. 1374-1403, 2013.
2. M. Malvezzi, P. Bertuccio, F. Levi, C. La Vecchia, and E. Negri, "European cancer mortality predictions for the year 2014," Annals of Oncology, vol. 25, no. 8, pp. 1650-1656, 2014.
3. R. Siegel, J.Ma, Z. Zou, and A. Jemal, "Cancer statistics, 2014," CA Cancer Journal for Clinicians, vol. 64, no. 1, pp. 9-29, 2014.
4. S. B. Jones, "Cancer in the developing world: a call to action," British Medical Journal, vol. 319, no. 7208, pp. 505-508, 1999.
5. M. Pereira, B. Peleteiro, S. Capewell, K. Bennett, A. Azevedo, and N. Lunet, "Changing patterns of cardiovascular diseases and cancer mortality in Portugal, 1980-2010.," BMC Public Health, vol. 12, article 1126, 2012.
6. R. Siegel, D. Naishadham, and A. Jemal, "Cancer statistics for Hispanics/Latinos, 2012," CA Cancer Journal for Clinicians, vol. 62, no. 5, pp. 283-298, 2012.
7. N. J. Kang, S. H. Shin, H. J. Lee, and K.W. Lee, "Polyphenols as small molecular inhibitors of signaling cascades in carcinogenesis," Pharmacology &Therapeutics, vol. 130, no. 3, pp. 310-324, 2011.
8. S. Mena, A. Ortega, and J. M. Estrela, "Oxidative stress in environmental-induced carcinogenesis," Mutation Research - Genetic Toxicology and EnvironmentalMutagenesis, vol. 674, no. 1-2, pp. 36-44, 2009.
9. B. N. Ames, M. K. Shigenaga, and T. M. Hagen, "Oxidants, antioxidants, and the degenerative diseases of aging," Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 17, pp. 7915-7922, 1993.
10. S. Quideau, D. Deffieux, C. Douat-Casassus, and L. Pouységu, "Plant polyphenols: chemical properties, biological activities, and synthesis," Angewandte Chemie - International Edition, vol. 50, no. 3, pp. 586-621, 2011.
11. L. Bravo, "Polyphenols: chemistry, dietary sources,metabolism, and nutritional significance," Nutrition Reviews, vol. 56, no. 11, pp. 317-333, 1998.
12. S. M. Poulose, N. Thangthaeng, M. G. Miller, and B. Shukitt-Hale, "Effects of pterostilbene and resveratrol on brain and behavior," Neurochemistry International, vol. 89, pp. 227-233, 2015.
13. J. Dai and R. J. Mumper, "Plant phenolics: extraction, analysis and their antioxidant and anticancer properties,"Molecules, vol. 15, no. 10, pp. 7313-7352, 2010.
14. Y.H. Li, Y. B. Niu, Y. Sun et al., "Role of phytochemicals in colorectal cancer prevention," World Journal of Gastroenterology, vol. 21, no. 31, pp. 9262-9272, 2015.
15. J. A. Nichols and S. K. Katiyar, "Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms," Archives of Dermatological Research, vol. 302, no. 2, pp. 71-83, 2010.
16. T. Shen, X.-N. Wang, and H.-X. Lou, "Natural stilbenes: an overview," Natural Product Reports, vol. 26, no. 7, pp. 916-935, 2009.
17. C. Rivière, A. D. Pawlus, and J.-M. Mérillon, "Natural stilbenoids: distribution in the plant kingdom and chemotaxonomic interest in Vitaceae," Natural Product Reports, vol. 29, no. 11, pp. 1317-1333, 2012.
18. M. Jang, L. Cai, G. O. Udeani et al., "Cancer chemopreventive activity of resveratrol, a natural product derived from grapes," Science, vol. 275, no. 5297, pp. 218-220, 1997.
19. M. B. Sporn, "Carcinogenesis and cancer: different perspectives on the same disease," Cancer Research, vol. 51, part 1, no. 23, pp. 6215-6218, 1991.
20. M. Asensi, A. Ortega, S. Mena, F. Feddi, and J. M. Estrela, "Natural polyphenols in cancer therapy," Critical Reviews in Clinical Laboratory Sciences, vol. 48, no. 5-6, pp. 197-216, 2011.
21. P. Langcake and R. J. Pryce, "The production of resveratrol by Vitis vinifera and other members of the Vitaceae as a response to infection or injury," Physiological Plant Pathology, vol. 9, no. 1, pp. 77-86, 1976.
22. A. Chatterjee, A. Ronghe, B. Singh,N. K. Bhat, J. Chen, and H. K. Bhat, "antioxidants exhibit chemopreventive characteristics through the regulation of CNC b-Zip transcription factors in estrogen-induced breast carcinogenesis," Journal of Biochemical and Molecular Toxicology, vol. 28, no. 12, pp. 529-538, 2014.
23. A. Malhotra, P. Nair, and D. K. Dhawan, "Study to evaluate molecular mechanics behind synergistic chemo-preventive effects of curcumin and resveratrol during lung carcinogenesis," PLoS ONE, vol. 9, no. 4,Article ID e93820, 2014.
24. F.Mazué, D. Delmas, G.Murillo, D. Saleiro, E. Limagne, and N. Latruffe, "Differential protective effects of red wine polyphenol extracts (RWEs) on colon carcinogenesis," Food&Function, vol. 5, no. 4, pp. 663-670, 2014.
25. J. H. Back, Y. Zhu, A. Calabro et al., "Resveratrol-mediated downregulation of rictor attenuates autophagic process and suppresses UV-induced skin carcinogenesis," Photochemistry and Photobiology, vol. 88, no. 5, pp. 1165-1172, 2012.
26. T.-C. Hsieh, C.-J. Yang, C.-Y. Lin, Y.-S. Lee, and J. M. Wu, "Control of stability of cyclin D1 by quinone reductase 2 in CWR22Rv1 prostate cancer cells," Carcinogenesis, vol. 33, no. 3, pp. 670-677, 2012.
27. C. Lin, D. R. Crawford, S. Lin et al., "Inducible COX-2-dependent apoptosis in human ovarian cancer cells," Carcinogenesis, vol. 32, no. 1, pp. 19-26, 2011.
28. D. Rajasekaran, J. Elavarasan,M. Sivalingam et al., "Resveratrol interferes with N-nitrosodiethylamine-induced hepatocellular carcinoma at early and advanced stages in male Wistar rats," Molecular Medicine Reports, vol. 4, no. 6, pp. 1211-1217, 2011.
29. S. Shrotriya, A. Tyagi, G. Deep et al., "Grape seed extract and resveratrol prevent 4-nitroquinoline 1-oxide induced oral tumorigenesis in mice by modulating AMPK activation and associated biological responses," Molecular Carcinogenesis, vol. 54, no. 4, pp. 291-300, 2015.
30. H. J. Kang, Y.-K. Youn, M.-K. Hong, and L. S. Kim, "Antiproliferation and redifferentiation in thyroid cancer cell lines by polyphenol phytochemicals," Journal of KoreanMedical Science, vol. 26, no. 7, pp. 893-899, 2011.
31. M.-F. Tsan, J. E. White, J. G. Maheshwari, and G. Chikkappa, "Anti-leukemia effect of resveratrol," Leukemia & Lymphoma, vol. 43, no. 5, pp. 983-987, 2002.
32. S. Temraz, D. Mukherji, and A. Shamseddine, "Potential targets for colorectal cancer prevention," International Journal of Molecular Sciences, vol. 14, no. 9, pp. 17279-17303, 2013.
33. D. Wang and R. N. Dubois, "The role of COX-2 in intestinal inflammation and colorectal cancer," Oncogene, vol. 29, no. 6, pp. 781-788, 2010.
34. K. Mosalpuria, C. Hall, S. Krishnamurthy et al., "Cyclooxygenase-2 expression in non-metastatic triple-negative breast cancer patients,"Molecular and ClinicalOncology, vol. 2, no. 5,pp. 845-850, 2014.
35. D. Wang, X.-Z. Guo, H.-Y. Li, J.-J. Zhao, X.-D. Shao, and C.-Y.Wu, "Prognostic significance of cyclooxygenase-2 protein in pancreatic cancer: a meta-analysis," Tumor Biology, vol. 35, no. 10, pp. 10301-10307, 2014.
36. A. Fernández-Alvarez, C. Llorente-Izquierdo, R. Mayoral et al., "Evaluation of epigenetic modulation of cyclooxygenase-2 as a prognostic marker for hepatocellular carcinoma," Oncogenesis, vol. 1, article e23, 2012.
37. C. Roubille, J.Martel-Pelletier, J.-M. Davy, B. Haraoui, and J.-P. Pelletier, "Cardiovascular adverse effects of anti-inflammatory drugs," Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, vol. 12, no. 1, pp. 55-67, 2013.
38. J. Jiao, T.-O. Ishikawa, D. S. Dumlao et al., "Targeted deletion and lipidomic analysis identify epithelial cell COX-2 as a major driver of chemically induced skin cancera," Molecular Cancer Research, vol. 12, no. 11, pp. 1677-1688, 2014.
39. L. J. Marnett, "Aspirin and the potential role of prostaglandins in colon cancer," Cancer Research, vol. 52, no. 20, pp. 5575-5589, 1992.
40. G. N. Levy, "Prostaglandin H synthases, nonsteroidal antiinflammatory drugs, and colon cancer," The FASEB Journal, vol. 11, no. 4, pp. 234-247, 1997.
41. A. Kitasato, T. Kuroki, T. Adachi et al., "A selective cyclooxygenase-2 inhibitor (etodolac) prevents spontaneous biliary tumorigenesis in a hamster bilioenterostomy model," European Surgical Research, vol. 52, no. 1-2, pp. 73-82, 2014.
42. A. Cianciulli, R. Calvello, P. Cavallo, T. Dragone, V. Carofiglio, and M. A. Panaro, "Modulation of NF-kappaB activation by resveratrol in LPS treated human intestinal cells results in downregulation of PGE2 production and COX-2 expression," Toxicology in Vitro, vol. 26, no. 7, pp. 1122-1128, 2012.
43. S. A. Schwartz, A. Hernandez, and B. Mark Evers, "The role of NF-κB/IκB proteins in cancer: implications for novel treatment strategies," Surgical Oncology, vol. 8, no. 3, pp. 143-153, 1999.
44. P. Viatour, M.-P. Merville, V. Bours, and A. Chariot, "Phosphorylation of NF-κB and IκB proteins: implications in cancer and inflammation," Trends in Biochemical Sciences, vol. 30, no. 1, pp. 43-52, 2005.
45. K. J. Campbell and N. D. Perkins, "Regulation of NF-kappaB function," Biochemical Society Symposium, vol. 73, pp. 165-180, 2006.
46. K. P. L. Bhat and J. M. Pezzuto, "Cancer chemopreventive activity of resveratrol," Annals of the New York Academy of Sciences, vol. 957, pp. 210-229, 2002.
47. C.O. Yi, B. T. Jeon, H. J. Shin et al., "Resveratrol activatesAMPK and suppresses LPS-induced NF-kappaB-dependent COX-2 activation in RAW 264.7 macrophage cells," Anatomy & Cell Biology, vol. 44, no. 3, pp. 194-203, 2011.
48. A. Bishayee, A. Waghray, K. F. Barnes et al., "Suppression of the inflammatory cascade is implicated in resveratrol chemoprevention of experimental hepatocarcinogenesis," Pharmaceutical Research, vol. 27, no. 6, pp. 1080-1091, 2010.
49. Y. Han, C. Jiang, J. Tang et al., "Resveratrol reduces morphine tolerance by inhibiting microglial activation via AMPK signalling," European Journal of Pain, vol. 18, no. 10, pp. 1458-1470, 2014.
50. S. Gürocak, E. Karabulut, N. Karadag, D. Ozgor, N. Ozkeles, and A. Bay Karabulut, "Preventive effects of resveratrol against azoxymethane induced damage in rat liver," Asian Pacific Journal of Cancer Prevention, vol. 14, no. 4, pp. 2367-2370, 2013.
51. M. Inglés, J. Gambini, M. G. Miguel et al., "PTEN mediates the antioxidant effect of resveratrol at nutritionally relevant concentrations," BioMed Research International, vol. 2014, Article ID 580852, 6 pages, 2014.
52. H. Akca, A. Demiray, M. Aslan, I. Acikbas, and O. Tokgun, "Tumour suppressor PTEN enhanced enzyme activity of GPx, SODand catalase by suppression of PI3K/AKT pathway in nonsmall cell lung cancer cell lines," Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 28, no. 3, pp. 539-544, 2013.
53. J. A. Sirerol, F. Feddi, S. Mena et al., "Topical treatment with pterostilbene, a natural phytoalexin, effectively protects hairless mice against UVB radiation-induced skin damage and carcinogenesis," Free Radical Biology and Medicine, vol. 85, pp. 1-11, 2015.
54. S.Mena,M. L. Rodríguez, X. Ponsoda, J. M. Estrela, M. Jäättela, and A. L. Ortega, "Pterostilbene-induced tumor cytotoxicity: a lysosomal membrane permeabilization-dependent mechanism," PLoS ONE, vol. 7, no. 9,Article ID e44524, 2012.
55. F. Casanova, J. Quarti, D. C. Ferraz da Costa, C. A. Ramos, J. L. Da Silva, and E. Fialho, "Resveratrol chemosensitizes breast cancer cells tomelphalan by cell cycle arrest," Journal of Cellular Biochemistry, vol. 113, no. 8, pp. 2586-2596, 2012.
56. X. D. Yu, J. L. Yang,W. L. Zhang, and D. X. Liu, "Resveratrol inhibits oral squamous cell carcinoma through induction of apoptosis and G2/M phase cell cycle arrest," Tumor Biology, 2015.
57. A. A. Gokbulut, E. Apohan, and Y. Baran, "Resveratrol and quercetin-induced apoptosis of human 232B4 chronic lymphocytic leukemia cells by activation of caspase-3 and cell cycle arrest," Hematology, vol. 18, no. 3, pp. 144-150, 2013.
58. R. Frazzi, R. Valli, I. Tamagnini, B. Casali, N. Latruffe, and F. Merli, "Resveratrol-mediated apoptosis of hodgkin lymphoma cells involves SIRT1 inhibition and FOXO3a hyperacetylation," International Journal of Cancer, vol. 132, no. 5, pp. 1013-1021, 2013.
59. S. Shankar, Q. Chen, I. Siddiqui, K. Sarva, and R. K. Srivastava, "Sensitization of TRAIL-resistant LNCaP cells by resveratrol (3, 4′, 5 tri-hydroxystilbene): molecular mechanisms and therapeutic potential," Journal of Molecular Signaling, vol. 2, article 7, 2014.
60. P. R. van Ginkel, M. B. Yan, S. Bhattacharya, A. S. Polans, and J. D. Kenealey, "Natural products induce a G protein-mediated calcium pathway activating p53 in cancer cells," Toxicology and Applied Pharmacology, 2015.
61. H.-Y. Lin, A. Shih, F. B. Davis et al., "Resveratrol induced serine phosphorylation of p53 causes apoptosis in a mutant p53 prostate cancer cell line," Journal of Urology, vol. 168, no. 2, pp. 748-755, 2002.
62. N. Singh, M. Nigam, V. Ranjan, R. Sharma, A. K. Balapure, and S. K. Rath, "Caspase mediated enhanced apoptotic action of cyclophosphamide-and resveratrol-treated MCF-7 cells," Journal of Pharmacological Sciences, vol. 109, no. 4, pp. 473-485, 2009.
63. L. Kai, S. K. Samuel, and A. S. Levenson, "Resveratrol enhances p53 acetylation and apoptosis in prostate cancer by inhibiting MTA1/NuRD complex," International Journal of Cancer, vol. 126, no. 7, pp. 1538-1548, 2010.
64. I. M. Kapetanovic, M. Muzzio, Z. Huang, T. N. Thompson, and D. L. McCormick, "Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats," Cancer Chemotherapy and Pharmacology, vol. 68, no. 3, pp. 593-601, 2011.
65. H.-S. Lin, B.-D. Yue, and P. C. Ho, "Determination of pterostilbene in rat plasma by a simple HPLC-UV method and its application in pre-clinical pharmacokinetic study," Biomedical Chromatography, vol. 23, no. 12, pp. 1308-1315, 2009.
66. A. M. Rimando, M. Cuendet, C. Desmarchelier, R. G. Mehta, J. M. Pezzuto, and S. O. Duke, "Cancer chemopreventive and antioxidant activities of pterostilbene, a naturally occurring analogue of resveratrol," Journal of Agricultural and Food Chemistry, vol. 50, no. 12, pp. 3453-3457, 2002.
67. L. A. Stivala, M. Savio, F. Carafoli et al., "Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol," The Journal of Biological Chemistry, vol. 276, no. 25, pp. 22586-22594, 2001.
68. D. McCormack and D. McFadden, "A review of pterostilbene antioxidant activity and disease modification," Oxidative Medicine and Cellular Longevity, vol. 2013, Article ID 575482, 15 pages, 2013.
69. P. Ferrer, M. Asensi, R. Segarra et al., "Association between pterostilbene and quercetin inhibits metastatic activity of B16 melanoma," Neoplasia, vol. 7, no. 1, pp. 37-47, 2005.
70. C. M. Remsberg, J. A. Yáñez, Y. Ohgami, K. R. Vega-Villa, A. M. Rimando, and N. M. Davies, "Pharmacometrics of pterostilbene: preclinical pharmacokinetics and metabolism, anticancer, antiinflammatory, antioxidant and analgesic activity," Phytotherapy Research, vol. 22, no. 2, pp. 169-179, 2008.
71. M. Tolomeo, S. Grimaudo, A. Di Cristina et al., "Pterostilbene and 3′-hydroxypterostilbene are effective apoptosis-inducing agents inMDR and BCR-ABL-expressing leukemia cells," International Journal of Biochemistry and Cell Biology, vol. 37, no. 8, pp. 1709-1726, 2005.
72. J. A. Alosi, D. E. McDonald, J. S. Schneider, A. R. Privette, and D. W. McFadden, "Pterostilbene inhibits breast cancer in vitro through mitochondrial depolarization and induction of caspase-dependent apoptosis," Journal of Surgical Research, vol. 161, no. 2, pp. 195-201, 2010.
73. Y. Wang, L. Ding, X. Wang et al., "Pterostilbene simultaneously induces apoptosis, cell cycle arrest and cyto-protective autophagy in breast cancer cells," American Journal of Translational Research, vol. 4, no. 1, pp. 44-51, 2012.
74. D. Moon, D. McCormack, D. McDonald, and D. McFadden, "Pterostilbene induces mitochondrially derived apoptosis in breast cancer cells in vitro," Journal of Surgical Research, vol. 180, no. 2, pp. 208-215, 2013.
75. J. G. Schneider, J. A. Alosi, D. E. McDonald, and D.W. McFadden, "Pterostilbene Inhibits Lung Cancer Through Induction of Apoptosis1," Journal of Surgical Research, vol. 161, no. 1, pp. 18-22, 2010.
76. R.-J. Chen, S.-J. Tsai, C.-T. Ho et al., "Chemopreventive effects of pterostilbene on urethane-induced lung carcinogenesis in mice via the inhibition of EGFR-mediated pathways and the induction of apoptosis and autophagy," Journal of Agricultural and Food Chemistry, vol. 60, no. 46, pp. 11533-11541, 2012.
77. A. Chakraborty, N. Gupta, K. Ghosh, and P. Roy, "In vitro evaluation of the cytotoxic, anti-proliferative and anti-oxidant properties of pterostilbene isolated from Pterocarpus marsupium," Toxicology in Vitro, vol. 24, no. 4, pp. 1215-1228, 2010.
78. D. E.McCormack, P.Mannal,D.McDonald, S.Tighe, J.Hanson, and D. McFadden, "Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo," Journal of Gastrointestinal Surgery, vol. 16, no. 6, pp. 1136-1143, 2012.
79. Y.-S.Chiou, M.-L. Tsai, K.Nagabhushanamet al., "Pterostilbene is more potent than resveratrol in preventing azoxymethane (AOM)-induced colon tumorigenesis via activation of the NF-E2-related factor 2 (Nrf2)-mediated antioxidant signaling pathway," Journal of Agricultural and Food Chemistry, vol. 59, no. 6, pp. 2725-2733, 2011.
80. S. Paul, A. M. Rimando, H. J. Lee, Y. Ji, B. S. Reddy, and N. Suh, "Anti-inflammatory action of pterostilbene is mediated through the p38 mitogen-activated protein kinase pathway in colon cancer cells," Cancer Prevention Research, vol. 2, no. 7, pp. 650-657, 2009.
81. N. Suh, S. Paul, X. Hao et al., "Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt foci formation in the azoxymethane-induced colon carcinogenesis model in rats," Clinical Cancer Research, vol. 13, no. 1, pp. 350-355, 2007.
82. M. Cichocki, J. Paluszczak, H. Szaefer, A. Piechowiak, A. M. Rimando, and W. Baer-Dubowska, "Pterostilbene is equally potent as resveratrol in inhibiting 12-O-tetradecanoylphorbol-13-acetate activated NFκB, AP-1, COX-2, and iNOS in mouse epidermis," Molecular Nutrition and Food Research, vol. 52, supplement 1, pp. S62-S70, 2008.
83. S. Dhar, A. Kumar, A. M. Rimando, X. Zhang, and A. S. Levenson, "Resveratrol and pterostilbene epigenetically restore PTEN expression by targeting oncomiRs of the miR-17 family in prostate cancer," Oncotarget, vol. 6, no. 29, pp. 27214-27226, 2015.
84. Y.-S. Chiou, M.-L. Tsai, Y.-J.Wang et al., "Pterostilbene inhibits colorectal aberrant crypt foci (ACF) and colon carcinogenesis via suppression of multiple signal transduction pathways in azoxymethane-treated mice," Journal of Agricultural and Food Chemistry, vol. 58, no. 15, pp. 8833-8841, 2010.
85. S. Paul, A. J. de Castro, H. J. Lee et al., "Dietary intake of pterostilbene, a constituent of blueberries, inhibits the betacatenin/p65 downstream signaling pathway and colon carcinogenesis in rats," Carcinogenesis, vol. 31,no. 7, pp. 1272-1278, 2010.
86. D. McCormack, J. Schneider, D. McDonald, and D. McFadden, "The antiproliferative effects of pterostilbene on breast cancer in vitro are via inhibition of constitutive and leptin-induced Janus kinase/signal transducer and activator of transcription activation,"The American Journal of Surgery, vol. 202, no. 5, pp. 541-544, 2011.
87. Y. Liu, L. Wang, Y. Wu et al., "Pterostilbene exerts antitumor activity against human osteosarcoma cells by inhibiting the JAK2/STAT3 signaling pathway," Toxicology, vol. 304, pp. 120-131, 2013.
88. R.-J. Chen, C.-T. Ho, and Y.-J. Wang, "Pterostilbene induces autophagy and apoptosis in sensitive and chemoresistant human bladder cancer cells," Molecular Nutrition and Food Research, vol. 54, no. 12, pp. 1819-1832, 2010.
89. A. Chakraborty, N. Bodipati, M. K. Demonacos, R. Peddinti, K. Ghosh, and P. Roy, "Long term induction by pterostilbene results in autophagy and cellular differentiation in MCF-7 cells via ROS dependent pathway," Molecular and Cellular Endocrinology, vol. 355, no. 1, pp. 25-40, 2012.
90. N. Mizushima and T. Yoshimori, "How to interpret LC3 immunoblotting," Autophagy, vol. 3, no. 6, pp. 542-545, 2007.
91. D. J. Klionsky, H. Abeliovich, P. Agostinis et al., "Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes," Autophagy, vol. 4, no. 2,pp. 151-175, 2008.
92. K. Siedlecka-Kroplewska, A. Jozwik, W. Boguslawski et al., "Pterostilbene induces accumulation of autophagic vacuoles followed by cell death inHL60 human leukemia cells," Journal of Physiology and Pharmacology, vol. 64, no. 5, pp. 545-556, 2013.
93. J. A. Magee, E. Piskounova, and S. J. Morrison, "Cancer stem cells: impact, heterogeneity, and uncertainty," Cancer Cell, vol. 21, no. 3, pp. 283-296, 2012.
94. L. V. Nguyen, R. Vanner, P. Dirks, and C. J. Eaves, "Cancer stem cells: an evolving concept," Nature Reviews Cancer, vol. 12, no. 2, pp. 133-143, 2012.
95. J. E. Visvader and G. J. Lindeman, "Cancer stem cells: current status and evolving complexities," Cell Stem Cell, vol. 10, no. 6, pp. 717-728, 2012.
96. K. Hagiwara, N. Kosaka, Y. Yoshioka, R.-U. Takahashi, F. Takeshita, and T. Ochiya, "Stilbene derivatives promote Ago2-dependent tumour-suppressive microRNA activity," Scientific Reports, vol. 2, article 314, 2012.
97. K.-K. Mak, A. T. H. Wu, W.-H. Lee et al., "Pterostilbene, a bioactive component of blueberries, suppresses the generation of breast cancer stem cells within tumor microenvironment and metastasis via modulating NF-κB/microRNA 448 circuit," Molecular Nutrition and Food Research, vol. 57, no. 7, pp. 1123-1134, 2013.
98. C.-M. Lee, Y.-H. Su, T.-T. Huynh et al., "BlueBerry isolate, pterostilbene, functions as a potential anticancer stem cell agent in suppressing irradiation-mediated enrichment of hepatoma stem cells," Evidence-Based Complementary and Alternative Medicine, vol. 2013, Article ID 258425, 9 pages, 2013.
99. T.-C. Hsieh, D. J. Bennett, Y.-S. Lee, E.Wu, and J.M.Wu, "In silico and biochemical analyses identify quinone reductase 2 as a target of piceatannol," Current Medicinal Chemistry, vol. 20, no. 33, pp. 4195-4202, 2013.
100. M.Murias,W. Jäger, N. Handler et al., "Antioxidant, prooxidant and cytotoxic activity of hydroxylated resveratrol analogues: structure-activity relationship," Biochemical Pharmacology, vol. 69, no. 6, pp. 903-912, 2005.
101. H. Piotrowska, M.Kucinska, and M.Murias, "Biological activity of piceatannol: leaving the shadow of resveratrol," Mutation Research/Reviews in Mutation Research, vol. 750, no. 1, pp. 60-82, 2012.
102. Z. Li, X. Yang, S. Dong, and X. Li, "DNa breakage induced by piceatannol and copper(II): mechanism and anticancer properties," Oncology Letters, vol. 3, no. 5, pp. 1087-1094, 2012.
103. A. S. Azmi, S. H. Bhat, and S. M. Hadi, "Resveratrol-Cu(II) induced DNA breakage in human peripheral lymphocytes: implications for anticancer properties," FEBS Letters, vol. 579, no. 14, pp. 3131-3135, 2005.
104. K. Ashikawa, S. Majumdar, S. Banerjee, A. C. Bharti, S. Shishodia, and B. B. Aggarwal, "Piceatannol inhibits TNFinduced NF-κB activation and NF-κB-mediated gene expression through suppression of IκBα kinase and p65 phosphorylation," Journal of Immunology, vol. 169, no. 11, pp. 6490-6497, 2002.
105. S. Islam, F. Hassan, M. M. Mu et al., "Piceatannol prevents lipopolysaccharide (LPS)-induced nitric oxide (NO) production and nuclear factor (NF)-kappaB activation by inhibiting IkappaB kinase (IKK)," Microbiology and Immunology, vol. 48, no. 10, pp. 729-736, 2004.
106. C.-Y. Jin, D.-O. Moon, K.-J. Lee et al., "Piceatannol attenuates lipopolysaccharide-induced NF-κB activation and NF-κBrelated proinflammatory mediators in BV2 microglia," Pharmacological Research, vol. 54, no. 6, pp. 461-467, 2006.
107. H.-H. Lee, S.-A. Park, I. Almazari, E.-H. Kim, H.-K. Na, and Y.-J. Surh, "Piceatannol induces heme oxygenase-1 expression in humanmammary epithelial cells through activation of AREdriven Nrf2 signaling," Archives of Biochemistry and Biophysics, vol. 501, no. 1, pp. 142-150, 2010.
108. E.-J. Park, H.-Y.Min, Y.-H.Ahn, C.-M. Bae, J.-H. Pyee, and S. K. Lee, "Synthesis and inhibitory effects of pinosylvin derivatives on prostaglandin E2 production in lipopolysaccharide-induced mouse macrophage cells," Bioorganic and Medicinal Chemistry Letters, vol. 14, no. 23, pp. 5895-5898, 2004.
109. E.-J. Park, H.-Y.Min, H.-J. Chung, Y.-H. Ahn, J.-H. Pyee, and S. K. Lee, "Pinosylvin suppresses LPS-stimulated inducible nitric oxide synthase expression via the MyD88-independent, but TRIF-dependent downregulation of IRF-3 signaling pathway in mousemacrophage cells," Cellular Physiology and Biochemistry, vol. 27, no. 3-4, pp. 353-362, 2011.
110. J. A. Edwards, M. Beck, C. Riegger, and J. Bausch, "Safety of resveratrol with examples for high purity, trans-resveratrol, resVida," Annals of the New York Academy of Sciences, vol. 1215, pp. 131-137, 2011.
111. L. D. Williams, G. A. Burdock, J. A. Edwards, M. Beck, and J. Bausch, "Safety studies conducted on high-purity transresveratrol in experimental animals," Food and Chemical Toxicology, vol. 47, no. 9, pp. 2170-2182, 2009.
112. J. A. Crowell, P. J. Korytko, R. L.Morrissey, T. D. Booth, and B. S. Levine, "Resveratrol-associated renal toxicity," Toxicological Sciences, vol. 82, no. 2, pp. 614-619, 2004.
113. L. Almeida,M. Vaz-da-Silva, A. Falcão et al., "Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers," Molecular Nutrition and Food Research, vol. 53, supplement 1, pp. S7-S15, 2009.
114. C. La Porte, N. Voduc, G. Zhang et al., "Steady-state pharmacokinetics and tolerability of trans-resveratrol 2000mg twice daily with food, quercetin and alcohol (Ethanol) in healthy human subjects," Clinical Pharmacokinetics, vol. 49, no. 7, pp. 449-454, 2010.
115. D. J. Boocock, G. E. S. Faust, K. R. Patel et al., "Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent," Cancer Epidemiology Biomarkers and Prevention, vol. 16, no. 6, pp. 1246-1252, 2007.
116. V. A. Brown, K. R. Patel, M. Viskaduraki et al., "Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis," Cancer Research, vol. 70, no. 22, pp. 9003-9011, 2010.
117. K. R. Patel, V. A. Brown, D. J. L. Jones et al., "Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients," Cancer Research, vol. 70, no. 19, pp. 7392-7399, 2010.
118. S. Priego, F. Feddi, P. Ferrer et al., "Natural polyphenols facilitate elimination of HT-29 colorectal cancer xenografts by chemoradiotherapy: a Bcl-2-and superoxide dismutase 2-dependent mechanism," Molecular Cancer Therapeutics, vol. 7, no. 10, pp. 3330-3342, 2008.
119. K. Li, S. J. Dias, A. M. Rimando et al., "Pterostilbene acts through metastasis-associated protein 1 to inhibit tumor growth, progression and metastasis in prostate cancer," PLoS ONE, vol. 8, no. 3, Article ID e57542, 2013.
120. M. J. Ruiz, M. Fernández, Y. Picó et al., "Dietary administration of high doses of pterostilbene and quercetin to mice is not toxic," Journal of Agricultural and Food Chemistry, vol. 57, no. 8, pp. 3180-3186, 2009.
121. D. M. Riche, C. L. McEwen, K. D. Riche et al., "Analysis of safety from a human clinical trial with pterostilbene," Journal of Toxicology, vol. 2013,Article ID 463595, 5 pages, 2013.
122. S. Gao and M. Hu, "Bioavailability challenges associated with development of anti-cancer phenolics," Mini-Reviews in Medicinal Chemistry, vol. 10, no. 6, pp. 550-567, 2010.
123. F. Visioli, C. A. De La Lastra, C. Andres-Lacueva et al., "Polyphenols and human health: a prospectus," Critical Reviews in Food Science and Nutrition, vol. 51, no. 6, pp. 524-546, 2011.
124. M. Asensi, I. Medina, A. Ortega et al., "Inhibition of cancer growth by resveratrol is related to its low bioavailability," Free Radical Biology and Medicine, vol. 33, no. 3, pp. 387-398, 2002.
125. D. M. Goldberg, J. Yan, and G. J. Soleas, "Absorption of three wine-related polyphenols in three different matrices by healthy subjects," Clinical Biochemistry, vol. 36, no. 1, pp. 79-87, 2003.
126. T.Walle, F. Hsieh,M. H. DeLegge, J. E. Oatis Jr., andU. K.Walle, "High absorption but very low bioavailability of oral resveratrol in humans,"DrugMetabolismandDisposition, vol. 32,no. 12,pp. 1377-1382, 2004.
127. T.Walle, "Bioavailability of resveratrol," Annals of the New York Academy of Sciences, vol. 1215, no. 1, pp. 9-15, 2011.
128. J.-F. Marier, P. Vachon, A. Gritsas, J. Zhang, J.-P. Moreau, and M. P. Ducharme, "Metabolism and disposition of resveratrol in rats: extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model," Journal of Pharmacology and ExperimentalTherapeutics, vol. 302, no. 1,pp. 369-373, 2002.
129. I. Alfaras, M. Emìlia Juan, and J. M. Planas, "Trans-resveratrol reduces precancerous colonic lesions in dimethylhydrazinetreated rats," Journal of Agricultural and Food Chemistry, vol. 58, no. 13, pp. 8104-8110, 2010.
130. M. Azorín-Ortuño, M. J. Yáñez-Gascón, F. Vallejo et al., "Metabolites and tissue distribution of resveratrol in the pig," Molecular Nutrition & Food Research, vol. 55, no. 8, pp. 1154-1168, 2011.
131. A. Burkon and V. Somoza, "Quantification of free and proteinbound trans-resveratrol metabolites and identification of transresveratrol-C/O-conjugated diglucuronides - two novel resveratrol metabolites in human plasma," Molecular Nutrition and Food Research, vol. 52, no. 5, pp. 549-557, 2008.
132. M. Rotches-Ribalta, C. Andres-Lacueva, R. Estruch, E. Escribano, and M. Urpi-Sarda, "Pharmacokinetics of resveratrol metabolic profile in healthy humans after moderate consumption of red wine and grape extract tablets," Pharmacological Research, vol. 66, no. 5, pp. 375-382, 2012.
133. C. Andres-Lacueva, M. T. MacArulla, M. Rotches-Ribalta et al., "Distribution of resveratrol metabolites in liver, adipose tissue, and skeletal muscle in rats fed different doses of this polyphenol," Journal of Agricultural andFoodChemistry, vol. 60, no. 19, pp. 4833-4840, 2012.
134. E.Wenzel, T. Soldo, H. Erbersdobler, andV. Somoza, "Bioactivity and metabolism of trans-resveratrol orally administered to Wistar rats,"Molecular Nutrition and Food Research, vol. 49, no. 5, pp. 482-494, 2005.
135. M. Azorín-Ortuño, M. J. Yañéz-Gascón, F. J. Pallarés et al., "Pharmacokinetic study of trans-resveratrol in adult pigs," Journal of Agricultural and Food Chemistry, vol. 58, no. 20, pp. 11165-11171, 2010.
136. M. Miksits, K. Wlcek, M. Svoboda et al., "Antitumor activity of resveratrol and its sulfated metabolites against human breast cancer cells," Planta Medica, vol. 75, no. 11, pp. 1227-1230, 2009.
137. J. Hoshino, E.-J. Park, T. P. Kondratyuk et al., "Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites," Journal of Medicinal Chemistry, vol. 53, no. 13, pp. 5033-5043, 2010.
138. C. E. Storniolo and J. J. Moreno, "Resveratrolmetabolites have an antiproliferative effect on intestinal epithelial cancer cells," Food Chemistry, vol. 134, no. 3, pp. 1385-1391, 2012.
139. D.-L. Lu, D.-J. Ding,W.-J. Yan et al., "Influence of glucuronidation and reduction modifications of resveratrol on its biological activities," ChemBioChem, vol. 14, no. 9, pp. 1094-1104, 2013.
140. E. Polycarpou, L. B. Meira, S. Carrington, E. Tyrrell, H. Modjtahedi, and M. A. Carew, "Resveratrol 3-O-d-glucuronide and resveratrol 4′-O-d-glucuronide inhibit colon cancer cell growth: evidence for a role of A3 adenosine receptors, cyclin D1 depletion, and G1 cell cycle arrest," Molecular Nutrition and Food Research, vol. 57, no. 10, pp. 1708-1717, 2013.
141. V. Aires, E. Limagne, A. K. Cotte, N. Latruffe, F. Ghiringhelli, andD.Delmas, "Resveratrolmetabolites inhibit human metastatic colon cancer cells progression and synergize with chemotherapeutic drugs to induce cell death,"Molecular Nutrition and Food Research, vol. 57, no. 7, pp. 1170-1181, 2013.
142. H. Sakamoto, H. Yokota, R. Kibe, Y. Sayama, and A. Yuasa, "Excretion of bisphenol A-glucuronide into the small intestine and deconjugation in the cecum of the rat," Biochimica et Biophysica Acta, vol. 1573, no. 2, pp. 171-176, 2002.
143. H. Kong, Y. Kim, Y. Lee et al., "Sulfate-conjugated methylprednisolone: evaluation as a colon-specific methylprednisolone prodrug and comparison with sulfate-conjugated prednisolone and dexamethasone," Journal of Drug Targeting, vol. 17,no. 2, pp. 159-167, 2009.
144. K. R. Patel, C. Andreadi, R. G. Britton et al., "Sulfate metabolites provide an intracellular pool for resveratrol generation and induce autophagy with senescence," Science Translational Medicine, vol. 5, no. 205,Article ID 205ra133, 2013.
145. A. A. Gakh, N. Y. Anisimova, M. V. Kiselevsky et al., "Dihydro-resveratrol - a potent dietary polyphenol," Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 20, pp. 6149-6151, 2010.
146. S. C. M. Yeo, P. C. Ho, and H.-S. Lin, "Pharmacokinetics of pterostilbene in Sprague-Dawley rats: the impacts of aqueous solubility, fasting, dose escalation, and dosing route on bioavailability," MolecularNutrition and Food Research, vol. 57,no. 6, pp. 1015-1025, 2013.
147. R.W. Dellinger, A.M. G. Garcia, and F. L.Meyskens Jr., "Differences in the glucuronidation of resveratrol and pterostilbene: altered enzyme specificity and potential gender differences," Drug Metabolism and Pharmacokinetics, vol. 29, no. 2, pp. 112-119, 2014.
148. J. M. Estrela, A. Ortega, S. Mena, M. L. Rodriguez, and M. Asensi, "Pterostilbene: biomedical applications," Critical Reviews in Clinical Laboratory Sciences, vol. 50, no. 3, pp. 65-78, 2013.
149. X. Shao, X. Chen, V. Badmaev, C.-T. Ho, and S. Sang, "Structural identification of mouse urinary metabolites of pterostilbene using liquid chromatography/tandemmass spectrometry," Rapid Communications inMass Spectrometry, vol. 24, no. 12, pp. 1770-1778, 2010.
150. M. Azzolini, M. La Spina, A. Mattarei, C. Paradisi, M. Zoratti, and L. Biasutto, "Pharmacokinetics and tissue distribution of pterostilbene in the rat,"Molecular Nutrition and Food Research, vol. 58, no. 11, pp. 2122-2132, 2014.
151. K. A. Roupe, J. A. Yáñez, X.W. Teng, and N. M. Davies, "Pharmacokinetics of selected stilbenes: rhapontigenin, piceatannol and pinosylvin in rats," Journal of Pharmacy and Pharmacology, vol. 58, no. 11, pp. 1443-1450, 2006.
152. K. Roupe, X. W. Teng, X. Fu, G. G. Meadows, and N. M. Davies, "Determination of piceatannol in rat serum and liver microsomes: pharmacokinetics and phase I and II biotransformation," Biomedical Chromatography, vol. 18,no. 8, pp.486-491, 2004.
153. Y. Setoguchi, Y. Oritani, R. Ito et al., "Absorption and metabolism of piceatannol in rats," Journal of Agricultural and Food Chemistry, vol. 62, no. 12, pp. 2541-2548, 2014.
154. K. Roupe, S. Halls, and N. M. Davies, "Determination and assay validation of pinosylvin in rat serum: application to drug metabolism and pharmacokinetics," Journal of Pharmaceutical and Biomedical Analysis, vol. 38, no. 1, pp. 148-154, 2005.
155. S. C. M. Yeo, W. Luo, J. Wu, P. C. Ho, and H.-S. Lin, "Quantification of pinosylvin in rat plasma by liquid chromatographytandem mass spectrometry: application to a pre-clinical pharmacokinetic study," Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, vol. 931, pp. 68-74, 2013.
156. M. Miksits, M. Sulyok, R. Schuhmacher, T. Szekeres, and W. Jäger, "In-vitro sulfation of piceatannol by human liver cytosol and recombinant sulfotransferases," Journal of Pharmacy and Pharmacology, vol. 61, no. 2, pp. 185-191, 2009.
157. H.-S. Lin, C. Tringali, C. Spatafora, C. Wu, and P. C. Ho, "A simple and sensitiveHPLC-UVmethod for the quantification of piceatannol analog trans-3,5,3′,4′-tetramethoxystilbene in rat plasma and its application for a pre-clinical pharmacokinetic study," Journal of Pharmaceutical and Biomedical Analysis, vol. 51, no. 3, pp. 679-684, 2010.
158. G. A. Potter, L. H. Patterson, E. Wanogho et al., "The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1b1," British Journal of Cancer, vol. 86, no. 5, pp. 774-778, 2002.
159. S. Sale, R. G. Tunstall, K. C. Ruparelia, G. A. Potter, W. P. Steward, and A. J. Gescher, "Comparison of the effects of the chemopreventive agent resveratrol and its synthetic analog trans 3,4,5,4′-tetramethoxystilbene (DMU-212) on adenoma development in the ApcMin+ mouse and cyclooxygenase-2 in human-derived colon cancer cells," International Journal of Cancer, vol. 115, no. 2, pp. 194-201, 2005.
160. J. Correa-Betanzo, E. Allen-Vercoe, J. McDonald, K. Schroeter, M.Corredig, and G. Paliyath, "Stability and biological activity of wild blueberry (Vaccinium angustifolium) polyphenols during simulated in vitro gastrointestinal digestion," Food Chemistry, vol. 165, pp. 522-531, 2014.
161. S. Karakaya, "Bioavailability of phenolic compounds," Critical Reviews in Food Science and Nutrition, vol. 44, no. 6, pp. 453-464, 2004.
162. B. B. Aggarwal, A. Bhardwaj, R. S. Aggarwal, N. P. Seeram, S. Shishodia, and Y. Takada, "Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies," Anticancer Research, vol. 24, no. 5, pp. 2783-2840, 2004.
163. C. Manach, A. Mazur, and A. Scalbert, "Polyphenols and prevention of cardiovascular diseases," Current Opinion in Lipidology, vol. 16, no. 1, pp. 77-84, 2005.
164. C.Manach, A. Scalbert, C.Morand, C. Rémésy, and L. Jiménez, "Polyphenols: food sources and bioavailability," American Journal of Clinical Nutrition, vol. 79, no. 5, pp. 727-747, 2004.
165. Y.-W. Shi, C.-P. Wang, L. Liu et al., "Antihyperuricemic and nephroprotective effects of resveratrol and its analogues in hyperuricemic mice," Molecular Nutrition and Food Research, vol. 56, no. 9, pp. 1433-1444, 2012.
166. T. Bohn, "Dietary factors affecting polyphenol bioavailability," Nutrition Reviews, vol. 72, no. 7, pp. 429-452, 2014.
167. T. T. H. Duong, B. Chami, A. C.McMahonet al., "Pre-treatment with the synthetic antioxidant T-butyl bisphenol protects cerebral tissues from experimental ischemia reperfusion injury," Journal of Neurochemistry, vol. 130, no. 6, pp. 733-747, 2014.
168. T. Szekeres, P. Saiko, M. Fritzer-Szekeres, B. Djavan, and W. Jäger, "Chemopreventive effects of resveratrol and resveratrol derivatives," Annals of the New York Academy of Sciences, vol. 1215, no. 1, pp. 89-95, 2011.
169. M.Murias, N.Handler, T. Erker et al., "Resveratrol analogues as selective cyclooxygenase-2 inhibitors: synthesis and structureactivity relationship," Bioorganic&Medicinal Chemistry, vol. 12, no. 21, pp. 5571-5578, 2004.
170. T. Perečko, V. Jančinová, K. Drábiková, R. Nosál', and J. Harmatha, "Structure-efficiency relationship in derivatives of stilbene. Comparison of resveratrol, pinosylvin and pterostilbene," Neuroendocrinology Letters, vol. 29, no. 5, pp. 802-805, 2008.
171. S.-Y.Kang, J. K. Lee, O. Choi et al., "Biosynthesis ofmethylated resveratrol analogs through the construction of an artificial biosynthetic pathway in E. coli," BMC Biotechnology, vol. 14, article 67, 2014.
172. G. Wang, X. Guo, H. Chen et al., "A resveratrol analog, phoyunbene B, induces G2/M cell cycle arrest and apoptosis in HepG2 liver cancer cells," Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 5, pp. 2114-2118, 2012.
173. S. Sale, R. D. Verschoyle, D. Boocock et al., "Pharmacokinetics in mice and growth-inhibitory properties of the putative cancer chemopreventive agent resveratrol and the synthetic analogue trans 3,4,5,4′-tetramethoxystilbene," British Journal of Cancer, vol. 90, no. 3, pp. 736-744, 2004.
174. L.M.Howells,D. P. Berry, P. J. Elliott et al., "Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases - safety, pharmacokinetics, and pharmacodynamics," Cancer Prevention Research, vol. 4, no. 9, pp. 1419-1425, 2011.
175. M. A. Noguer, A. B. Cerezo, E. D. Navarro, andM. C. Garcia-Parrilla, "Intake of alcohol-free red winemodulates antioxidant enzyme activities in a human intervention study," Pharmacological Research, vol. 65, no. 6, pp. 609-614, 2012.