Polyphenolic Phytochemicals in Cancer Prevention and Therapy: Bioavailability versus Bioefficacy

Journal of Medicinal Chemistry

Volumn 60, Issue 23, 2017, Pages 9413-9436

  Estrela, José M ^a   Mena, Salvador ^a   Obrador, Elena ^a   Benlloch, María ^b   Castellano, Gloria ^b   Salvador, Rosario ^a   Dellinger, Ryan W ^c  

^a UNIVERSITY OF VALENCIA   (Spain)

^b UNIVERSIDAD CATÓLICA DE VALENCIA SAN VICENTE MÁRTIR   (Spain)

^c Elysium Analytics Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; PLANT MEDICINAL PRODUCT; POLYPHENOL DERIVATIVE; POLYPHENOL;

ADVERSE DRUG REACTION; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER PREVENTION; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG FORMULATION; DRUG MECHANISM; DRUG METABOLISM; HUMAN; MALIGNANT NEOPLASM; NONHUMAN; STRUCTURE ACTIVITY RELATION; UNSPECIFIED SIDE EFFECT; ANIMAL; BIOAVAILABILITY; METABOLISM; NEOPLASM;

ANIMALS; ANTICARCINOGENIC AGENTS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; BIOLOGICAL AVAILABILITY; DRUG DELIVERY SYSTEMS; HUMANS; NEOPLASMS; PHYTOCHEMICALS; POLYPHENOLS;

EID: 85030791402     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.6b01026     Document Type: Article

References (237)

1. MedicineNet: Health and Medical Information Produced by Doctors; MedicinNet, Inc., 1996; http://www.medicinenet.com/script/main/hp.asp (accessed July 28, 2016).
2. World Health Organization; World Health Organization: Geneva, 2017; http://www.who.int/en/ (accessed Jul 28, 2016).
3. Greenwell, M.; Rahman, P. K. S. M. Medicinal Plants: Their Use in Anticancer Treatment Int. J. Pharm. Sci. Res. 2015, 6 (10) 4103-4112 10.13040/IJPSR.0975-8232.6(10).4103-12
4. Hosseini, A.; Ghorbani, A. Cancer Therapy with Phytochemicals: Evidence from Clinical Studies Avicenna J. Phytomed. 2015, 5 (2) 84-97 10.22038/ajp.2015.3872
5. Key, T. J. Fruit and Vegetables and Cancer Risk Br. J. Cancer 2011, 104 (1) 6-11 10.1038/sj.bjc.6606032
6. Wang, X.; Ouyang, Y.; Liu, J.; Zhu, M.; Zhao, G.; Bao, W.; Hu, F. B. Fruit and Vegetable Consumption and Mortality from All Causes, Cardiovascular Disease, and Cancer: Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies BMJ. 2014, 349, g4490 10.1136/bmj.g4490
7. Asensi, M.; Ortega, A.; Mena, S.; Feddi, F.; Estrela, J. M. Natural Polyphenols in Cancer Therapy Crit. Rev. Clin. Lab. Sci. 2011, 48 (5-6) 197-216 10.3109/10408363.2011.631268
8. Colomer, R.; Sarrats, A.; Lupu, R.; Puig, T. Natural Polyphenols and Their Synthetic Analogs as Emerging Anticancer Agents Curr. Drug Targets 2017, 18 (2) 147-159 10.2174/1389450117666160112113930
9. ClinicalTrials.gov; U.S. National Institutes of Health: Bethesda, MD, 2017; https://clinicaltrials.gov/ (accessed Jul 28, 2016).
10. Wang, J.; Tang, L.; Wang, J.-S. Biomarkers of Dietary Polyphenols in Cancer Studies: Current Evidence and Beyond Oxid. Med. Cell. Longevity 2015, 2015, 732302 10.1155/2015/732302
11. Maru, G. B.; Hudlikar, R. R.; Kumar, G.; Gandhi, K.; Mahimkar, M. B. Understanding the Molecular Mechanisms of Cancer Prevention by Dietary Phytochemicals: From Experimental Models to Clinical Trials World J. Biol. Chem. 2016, 7 (1) 88-99 10.4331/wjbc.v7.i1.88
12. Boyapati, S. M.; Shu, X.; Ruan, Z. X.; Dai, Q.; Cai, Q.; Gao, Y.; Zheng, W. Soyfood Intake and Breast Cancer Survival: A Followup of the Shanghai Breast Cancer Study Breast Cancer Res. Treat. 2005, 92 (1) 11-17 10.1007/s10549-004-6019-9
13. Swann, R.; Perkins, K. A.; Velentzis, L. S.; Ciria, C.; Dutton, S. J.; Mulligan, A. A.; Woodside, J. V.; Cantwell, M. M.; Leathem, A. J.; Robertson, C. E.; Dwek, M. V. The DietCompLyf Study: A Prospective Cohort Study of Breast Cancer Survival and Phytoestrogen Consumption Maturitas 2013, 75 (3) 232-240 10.1016/j.maturitas.2013.03.018
14. Kotecha, R.; Takami, A.; Espinoza, J. L. Dietary Phytochemicals and Cancer Chemoprevention: A Review of the Clinical Evidence Oncotarget 2016, 7, 52517-52529 10.18632/oncotarget.9593
15. Kroon, P. A.; Clifford, M. N.; Crozier, A.; Day, A. J.; Donovan, J. L.; Manach, C.; Williamson, G. How Should We Assess the Effects of Exposure to Dietary Polyphenols in Vitro? Am. J. Clin. Nutr. 2004, 80 (1) 15-21
16. Quideau, S.; Deffieux, D.; Douat-Casassus, C.; Pouységu, L. Plant Polyphenols: Chemical Properties, Biological Activities, and Synthesis Angew. Chem., Int. Ed. 2011, 50 (3) 586-621 10.1002/anie.201000044
17. McManus, J. P.; Davis, K. G.; Beart, J. E.; Gaffney, S. H.; Lilley, T. H.; Haslam, E. Polyphenol Interactions. Part 1. Introduction; Some Observations on the Reversible Complexation of Polyphenols with Proteins and Polysaccharides J. Chem. Soc., Perkin Trans. 2 1985, 9, 1429-1438 10.1039/p29850001429
18. Dai, J.; Mumper, R. J. Plant Phenolics: Extraction, Analysis and Their Antioxidant and Anticancer Properties Molecules 2010, 15 (10) 7313-7352 10.3390/molecules15107313
19. Manach, C.; Scalbert, A.; Morand, C.; Rémésy, C.; Jiménez, L. Polyphenols: Food Sources and Bioavailability Am. J. Clin. Nutr. 2004, 79 (5) 727-747
20. Tsao, R. Chemistry and Biochemistry of Dietary Polyphenols Nutrients 2010, 2 (12) 1231-1246 10.3390/nu2121231
21. Li, A.-N.; Li, S.; Zhang, Y.-J.; Xu, X.-R.; Chen, Y.-M.; Li, H.-B. Resources and Biological Activities of Natural Polyphenols Nutrients 2014, 6 (12) 6020-6047 10.3390/nu6126020
22. Amarowicz, R.; Carle, R.; Dongowski, G.; Durazzo, A.; Galensa, R.; Kammerer, D.; Maiani, G.; Piskula, M. K. Influence of Postharvest Processing and Storage on the Content of Phenolic Acids and Flavonoids in Foods Mol. Nutr. Food Res. 2009, 53, S151-S183 10.1002/mnfr.200700486
23. Visioli, F.; Alarcon De La Lastra, C.; Andres-Lacueva, C.; Aviram, M.; Calhau, C.; Cassano, A.; D'Archivio, M.; Faria, A.; Favé, G.; Fogliano, V.; Llorach, R.; Vitaglione, P.; Zoratti, M.; Edeas, M. Polyphenols and Human Health: A Prospectus Crit. Rev. Food Sci. Nutr. 2011, 51 (6) 524-546 10.1080/10408391003698677
24. McSweeney, M.; Seetharaman, K. State of Polyphenols in the Drying Process of Fruits and Vegetables Crit. Rev. Food Sci. Nutr. 2015, 55 (5) 660-669 10.1080/10408398.2012.670673
25. Tessitore, L.; Davit, A.; Sarotto, I.; Caderni, G. Resveratrol Depresses the Growth of Colorectal Aberrant Crypt Foci by Affecting Bax and p21(CIP) Expression Carcinogenesis 2000, 21 (8) 1619-1622 10.1093/carcin/21.5.619
26. Li, Z. G.; Hong, T.; Shimada, Y.; Komoto, I.; Kawabe, A.; Ding, Y.; Kaganoi, J.; Hashimoto, Y.; Imamura, M. Suppression of N-Nitrosomethylbenzylamine (NMBA)-Induced Esophageal Tumorigenesis in F344 Rats by Resveratrol Carcinogenesis 2002, 23 (9) 1531-1536 10.1093/carcin/23.9.1531
27. Banerjee, S.; Bueso-Ramos, C.; Aggarwal, B. B. 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. 2002, 62 (17) 4945-4954
28. Singh, B.; Shoulson, R.; Chatterjee, A.; Ronghe, A.; Bhat, N. K.; Dim, D. C.; Bhat, H. K. Resveratrol Inhibits Estrogen-Induced Breast Carcinogenesis through Induction of NRF2-Mediated Protective Pathways Carcinogenesis 2014, 35 (8) 1872-1880 10.1093/carcin/bgu120
29. Tsai, M.-L.; Lai, C.-S.; Chang, Y.-H.; Chen, W.-J.; Ho, C.-T.; Pan, M.-H. Pterostilbene, a Natural Analogue of Resveratrol, Potently Inhibits 7,12-Dimethylbenz[a]anthracene (DMBA)/12-O-Tetradecanoylphorbol-13-Acetate (TPA)-Induced Mouse Skin Carcinogenesis Food Funct. 2012, 3 (11) 1185-1194 10.1039/c2fo30105a
30. Su, C.-M.; Lee, W.-H.; Wu, A. T. H.; Lin, Y.-K.; Wang, L.-S.; Wu, C.-H.; Yeh, C.-T. Pterostilbene Inhibits Triple-Negative Breast Cancer Metastasis via Inducing microRNA-205 Expression and Negatively Modulates Epithelial-to-Mesenchymal Transition J. Nutr. Biochem. 2015, 26 (6) 675-685 10.1016/j.jnutbio.2015.01.005
31. Sirerol, J. A.; Feddi, F.; Mena, S.; Rodriguez, M. L.; Sirera, P.; Aupí, M.; Pérez, S.; Asensi, M.; Ortega, A.; Estrela, J. M. Topical Treatment with Pterostilbene, a Natural Phytoalexin, Effectively Protects Hairless Mice against UVB Radiation-Induced Skin Damage and Carcinogenesis Free Radical Biol. Med. 2015, 85, 1-11 10.1016/j.freeradbiomed.2015.03.027
32. Dhar, S.; Kumar, A.; Zhang, L.; Rimando, A. M.; Lage, J. M.; Lewin, J. R.; Atfi, A.; Zhang, X.; Levenson, A. S. Dietary Pterostilbene Is a Novel MTA1-Targeted Chemopreventive and Therapeutic Agent in Prostate Cancer Oncotarget 2016, 7, 18469-18484 10.18632/oncotarget.7841
33. Benlloch, M.; Obrador, E.; Valles, S. L.; Rodriguez, M. L.; Sirerol, J. A.; Alcácer, J.; Pellicer, J. A.; Salvador, R.; Cerdá, C.; Sáez, G. T.; Estrela, J. M. Pterostilbene Decreases the Antioxidant Defenses of Aggressive Cancer Cells In Vivo: A Physiological Glucocorticoids- and Nrf2-Dependent Mechanism Antioxid. Redox Signaling 2016, 24 (17) 974-990 10.1089/ars.2015.6437
34. Escutia-Gutiérrez, R.; Reyes-Esparza, J.; Rodriguez-Fragoso, L. Effect of Gallic Acid on Preneoplastic Liver Lesions in Vivo FASEB J. 2016, 30, 1268.7
35. Phan, A. N. H.; Hua, T. N. M.; Kim, M.-K.; Vo, V. T. A.; Choi, J.-W.; Kim, H.-W.; Rho, J. K.; Kim, K. W.; Jeong, Y. Gallic Acid Inhibition of Src-Stat3 Signaling Overcomes Acquired Resistance to EGF Receptor Tyrosine Kinase Inhibitors in Advanced Non-Small Cell Lung Cancer Oncotarget 2016, 7, 54702-54713 10.18632/oncotarget.10581
36. Liang, C.; Zhang, X.; Li, H.; Tao, Y.; Tao, L.; Yang, Z.; Zhou, X.; Shi, Z.; Tao, H. Gallic Acid Induces the Apoptosis of Human Osteosarcoma Cells in Vitro and in Vivo via the Regulation of Mitogen-Activated Protein Kinase Pathways Cancer Biother.Radiopharm. 2012, 27 (10) 701-710 10.1089/cbr.2012.1245
37. Chung, T.-W.; Moon, S.-K.; Chang, Y.-C.; Ko, J.-H.; Lee, Y.-C.; Cho, G.; Kim, S.-H.; Kim, J.-G.; Kim, C.-H. Novel and Therapeutic Effect of Caffeic Acid and Caffeic Acid Phenyl Ester on Hepatocarcinoma Cells: Complete Regression of Hepatoma Growth and Metastasis by Dual Mechanism FASEB J. 2004, 18 (14) 1670-1681 10.1096/fj.04-2126com
38. Masuelli, L.; Benvenuto, M.; Fantini, M.; Marzocchella, L.; Sacchetti, P.; Di Stefano, E.; Tresoldi, I.; Izzi, V.; Bernardini, R.; Palumbo, C.; Mattei, M.; Lista, F.; Galvano, F.; Modesti, A.; Bei, R. Curcumin Induces Apoptosis in Breast Cancer Cell Lines and Delays the Growth of Mammary Tumors in Neu Transgenic Mice J. Biol. Regul. Homeost. Agents 2013, 27 (1) 105-119
39. Chun, K.-S.; Keum, Y.-S.; Han, S. S.; Song, Y.-S.; Kim, S.-H.; Surh, Y.-J. Curcumin Inhibits Phorbol Ester-Induced Expression of Cyclooxygenase-2 in Mouse Skin through Suppression of Extracellular Signal-Regulated Kinase Activity and NF-kappaB Activation Carcinogenesis 2003, 24 (9) 1515-1524 10.1093/carcin/bgg107
40. Lirdprapamongkol, K.; Sakurai, H.; Kawasaki, N.; Choo, M.-K.; Saitoh, Y.; Aozuka, Y.; Singhirunnusorn, P.; Ruchirawat, S.; Svasti, J.; Saiki, I. Vanillin Suppresses in Vitro Invasion and in Vivo Metastasis of Mouse Breast Cancer Cells Eur. J. Pharm. Sci. 2005, 25 (1) 57-65 10.1016/j.ejps.2005.01.015
41. Shahan Shahriar, S. M.; Mohsin Ali, S. M.; Jesmin, M.; Khairul Islam, M.; Mondal, S. In Vivo Anticancer Activity of Vanillin, Benzophenone and Acetophenone Thiosemicarbazones on Swiss Albino Mice J. Coast. Life Med. 2014, 2 (10) 811-816 10.12980/JCLM.2.201414B35
42. Hamdi, H. K.; Castellon, R. Oleuropein, a Non-Toxic Olive Iridoid, Is an Anti-Tumor Agent and Cytoskeleton Disruptor Biochem. Biophys. Res. Commun. 2005, 334 (3) 769-778 10.1016/j.bbrc.2005.06.161
43. Aisha, A. F. A.; Abu-Salah, K. M.; Ismail, Z.; Majid, A. M. S. A. In Vitro and in Vivo Anti-Colon Cancer Effects of Garcinia Mangostana Xanthones Extract BMC Complementary Altern. Med. 2012, 12, 104 10.1186/1472-6882-12-104
44. Kosem, N.; Ichikawa, K.; Utsumi, H.; Moongkarndi, P. In Vivo Toxicity and Antitumor Activity of Mangosteen Extract J. Nat. Med. 2013, 67 (2) 255-263 10.1007/s11418-012-0673-8
45. Shibata, M.-A.; Iinuma, M.; Morimoto, J.; Kurose, H.; Akamatsu, K.; Okuno, Y.; Akao, Y.; Otsuki, Y. α-Mangostin Extracted from the Pericarp of the Mangosteen (Garcinia Mangostana Linn) Reduces Tumor Growth and Lymph Node Metastasis in an Immunocompetent Xenograft Model of Metastatic Mammary Cancer Carrying a p53 Mutation BMC Med. 2011, 9, 69 10.1186/1741-7015-9-69
46. Xu, Q.; Ma, J.; Lei, J.; Duan, W.; Sheng, L.; Chen, X.; Hu, A.; Wang, Z.; Wu, Z.; Wu, E.; Ma, Q.; Li, X. α-Mangostin Suppresses the Viability and Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells by Downregulating the PI3K/Akt Pathway BioMed Res. Int. 2014, 2014, 546353 10.1155/2014/546353
47. Liang, G.; Tang, A.; Lin, X.; Li, L.; Zhang, S.; Huang, Z.; Tang, H.; Li, Q. Q. Green Tea Catechins Augment the Antitumor Activity of Doxorubicin in an in Vivo Mouse Model for Chemoresistant Liver Cancer Int. J. Oncol. 2010, 37 (1) 111-123 10.3892/ijo-00000659
48. Li, S.; Wu, L.; Feng, J.; Li, J.; Liu, T.; Zhang, R.; Xu, S.; Cheng, K.; Zhou, Y.; Zhou, S.; Kong, R.; Chen, K.; Wang, F.; Xia, Y.; Lu, J.; Zhou, Y.; Dai, W.; Guo, C. In Vitro and in Vivo Study of Epigallocatechin-3-Gallate-Induced Apoptosis in Aerobic Glycolytic Hepatocellular Carcinoma Cells Involving Inhibition of Phosphofructokinase Activity Sci. Rep. 2016, 6, 28479 10.1038/srep28479
49. Gu, Y.; Zhu, C.-F.; Iwamoto, H.; Chen, J.-S. Genistein Inhibits Invasive Potential of Human Hepatocellular Carcinoma by Altering Cell Cycle, Apoptosis, and Angiogenesis World J. Gastroenterol. 2005, 11 (41) 6512-6517 10.3748/wjg.v11.i41.6512
50. Chodon, D.; Banu, S. M.; Padmavathi, R.; Sakthisekaran, D. Inhibition of Cell Proliferation and Induction of Apoptosis by Genistein in Experimental Hepatocellular Carcinoma Mol. Cell. Biochem. 2007, 297 (1-2) 73-80 10.1007/s11010-006-9324-2
51. Tatsuta, M.; Iishi, H.; Baba, M.; Yano, H.; Uehara, H.; Nakaizumi, A. Attenuation by Genistein of Sodium-Chloride-Enhanced Gastric Carcinogenesis Induced by N-Methyl-N'-nitro-N-Nitrosoguanidine in Wistar Rats Int. J. Cancer 1999, 80 (3) 396-399 10.1002/(SICI)1097-0215(19990129)80:3<396::AID-IJC10>3.0.CO;2-1
52. Chan, S.-T.; Yang, N.-C.; Huang, C.-S.; Liao, J.-W.; Yeh, S.-L. Quercetin Enhances the Antitumor Activity of Trichostatin A through Upregulation of p53 Protein Expression in Vitro and in Vivo PLoS One 2013, 8 (1) e54255 10.1371/journal.pone.0054255
53. Angst, E.; Park, J. L.; Moro, A.; Lu, Q.-Y.; Lu, X.; Li, G.; King, J.; Chen, M.; Reber, H. A.; Go, V. L. W.; Eibl, G.; Hines, O. J. The Flavonoid Quercetin Inhibits Pancreatic Cancer Growth in Vitro and in Vivo Pancreas 2013, 42 (2) 223-229 10.1097/MPA.0b013e318264ccae
54. Kuo, W.-T.; Tsai, Y.-C.; Wu, H.-C.; Ho, Y.-J.; Chen, Y.-S.; Yao, C.-H.; Yao, C.-H. Radiosensitization of Non-Small Cell Lung Cancer by Kaempferol Oncol. Rep. 2015, 34 (5) 2351-2356 10.3892/or.2015.4204
55. Song, H.; Bao, J.; Wei, Y.; Chen, Y.; Mao, X.; Li, J.; Yang, Z.; Xue, Y. Kaempferol Inhibits Gastric Cancer Tumor Growth: An in Vitro and in Vivo Study Oncol. Rep. 2015, 33 (2) 868-874 10.3892/or.2014.3662
56. Shukla, S.; Gupta, S. Molecular Targets for Apigenin-Induced Cell Cycle Arrest and Apoptosis in Prostate Cancer Cell Xenograft Mol. Cancer Ther. 2006, 5 (4) 843-852 10.1158/1535-7163.MCT-05-0370
57. Kaur, P.; Shukla, S.; Gupta, S. Plant Flavonoid Apigenin Inactivates Akt to Trigger Apoptosis in Human Prostate Cancer: An in Vitro and in Vivo Study Carcinogenesis 2008, 29 (11) 2210-2217 10.1093/carcin/bgn201
58. Pandey, M.; Kaur, P.; Shukla, S.; Abbas, A.; Fu, P.; Gupta, S. Plant Flavone Apigenin Inhibits HDAC and Remodels Chromatin to Induce Growth Arrest and Apoptosis in Human Prostate Cancer Cells: In Vitro and in Vivo Study Mol. Carcinog. 2012, 51 (12) 952-962 10.1002/mc.20866
59. Chian, S.; Thapa, R.; Chi, Z.; Wang, X. J.; Tang, X. Luteolin Inhibits the Nrf2 Signaling Pathway and Tumor Growth in Vivo Biochem. Biophys. Res. Commun. 2014, 447 (4) 602-608 10.1016/j.bbrc.2014.04.039
60. Majumdar, D.; Jung, K.-H.; Zhang, H.; Nannapaneni, S.; Wang, X.; Amin, A. R. M. R.; Chen, Z.; Chen, Z. G.; Shin, D. M. Luteolin Nanoparticle in Chemoprevention: In Vitro and in Vivo Anticancer Activity Cancer Prev. Res. 2014, 7 (1) 65-73 10.1158/1940-6207.CAPR-13-0230
61. Cook, M. T.; Liang, Y.; Besch-Williford, C.; Goyette, S.; Mafuvadze, B.; Hyder, S. M. Luteolin Inhibits Progestin-Dependent Angiogenesis, Stem Cell-like Characteristics, and Growth of Human Breast Cancer Xenografts SpringerPlus 2015, 4, 444 10.1186/s40064-015-1242-x
62. Dhanapal, S.; Ganapathy, E. An in Vitro and in Vivo Study of Antitumor Effects of Naringenin on Gastric Cancer Model FASEB J. 2013, 27, lb192
63. Zhang, J.; Wu, D.; Vikash; Song, J.; Wang, J.; Yi, J.; Dong, W. Hesperetin Induces the Apoptosis of Gastric Cancer Cells via Activating Mitochondrial Pathway by Increasing Reactive Oxygen Species Dig. Dis. Sci. 2015, 60 (10) 2985-2995 10.1007/s10620-015-3696-7
64. Hafeez, B. B.; Siddiqui, I. A.; Asim, M.; Malik, A.; Afaq, F.; Adhami, V. M.; Saleem, M.; Din, M.; Mukhtar, H. A Dietary Anthocyanidin Delphinidin Induces Apoptosis of Human Prostate Cancer PC3 Cells in Vitro and in Vivo: Involvement of Nuclear Factor-kappaB Signaling Cancer Res. 2008, 68 (20) 8564-8572 10.1158/0008-5472.CAN-08-2232
65. Wang, L.-S.; Hecht, S. S.; Carmella, S. G.; Yu, N.; Larue, B.; Henry, C.; McIntyre, C.; Rocha, C.; Lechner, J. F.; Stoner, G. D. Anthocyanins in Black Raspberries Prevent Esophageal Tumors in Rats Cancer Prev. Res. 2009, 2 (1) 84-93 10.1158/1940-6207.CAPR-08-0155
66. Wu, C.-H.; Ho, Y.-S.; Tsai, C.-Y.; Wang, Y.-J.; Tseng, H.; Wei, P.-L.; Lee, C.-H.; Liu, R.-S.; Lin, S.-Y. In Vitro and in Vivo Study of Phloretin-Induced Apoptosis in Human Liver Cancer Cells Involving Inhibition of Type II Glucose Transporter Int. J. Cancer 2009, 124 (9) 2210-2219 10.1002/ijc.24189
67. Fernando, W.; Coombs, M. R. P.; Hoskin, D. W.; Rupasinghe, H. P. V. Docosahexaenoic Acid-Acylated Phloridzin, a Novel Polyphenol Fatty Acid Ester Derivative, Is Cytotoxic to Breast Cancer Cells Carcinogenesis 2016, 37 (10) 1004-1013 10.1093/carcin/bgw087
68. Ferrer, P.; Asensi, M.; Segarra, R.; Ortega, A.; Benlloch, M.; Obrador, E.; Varea, M. T.; Asensio, G.; Jordá, L.; Estrela, J. M. Association between Pterostilbene and Quercetin Inhibits Metastatic Activity of B16 Melanoma Neoplasia N. Y. N 2005, 7 (1) 37-47 10.1593/neo.04337
69. Harper, C. E.; Cook, L. M.; Patel, B. B.; Wang, J.; Eltoum, I. A.; Arabshahi, A.; Shirai, T.; Lamartiniere, C. A. Genistein and Resveratrol, Alone and in Combination, Suppress Prostate Cancer in SV-40 Tag Rats Prostate 2009, 69 (15) 1668-1682 10.1002/pros.21017
70. Zhou, D.-H.; Wang, X.; Yang, M.; Shi, X.; Huang, W.; Feng, Q. Combination of Low Concentration of (-)-Epigallocatechin Gallate (EGCG) and Curcumin Strongly Suppresses the Growth of Non-Small Cell Lung Cancer in Vitro and in Vivo through Causing Cell Cycle Arrest Int. J. Mol. Sci. 2013, 14 (6) 12023-12036 10.3390/ijms140612023
71. Somers-Edgar, T. J.; Scandlyn, M. J.; Stuart, E. C.; Le Nedelec, M. J.; Valentine, S. P.; Rosengren, R. J. The Combination of Epigallocatechin Gallate and Curcumin Suppresses ER Alpha-Breast Cancer Cell Growth in Vitro and in Vivo Int. J. Cancer 2008, 122 (9) 1966-1971 10.1002/ijc.23328
72. Anand, K.; Sarkar, A.; Kumar, A.; Ambasta, R. K.; Kumar, P. Combinatorial Antitumor Effect of Naringenin and Curcumin Elicit Angioinhibitory Activities in Vivo Nutr. Cancer 2012, 64 (5) 714-724 10.1080/01635581.2012.686648
73. Amin, A. R. M. R.; Wang, D.; Zhang, H.; Peng, S.; Shin, H. J. C.; Brandes, J. C.; Tighiouart, M.; Khuri, F. R.; Chen, Z. G.; Shin, D. M. Enhanced Anti-Tumor Activity by the Combination of the Natural Compounds (-)-Epigallocatechin-3-Gallate and Luteolin: Potential Role of p53 J. Biol. Chem. 2010, 285 (45) 34557-34565 10.1074/jbc.M110.141135
74. Masuelli, L.; Di Stefano, E.; Fantini, M.; Mattera, R.; Benvenuto, M.; Marzocchella, L.; Sacchetti, P.; Focaccetti, C.; Bernardini, R.; Tresoldi, I.; Izzi, V.; Mattei, M.; Frajese, G. V.; Lista, F.; Modesti, A.; Bei, R. Resveratrol Potentiates the in Vitro and in Vivo Anti-Tumoral Effects of Curcumin in Head and Neck Carcinomas Oncotarget 2014, 5 (21) 10745-10762 10.18632/oncotarget.2534
75. Majumdar, A. P. N.; Banerjee, S.; Nautiyal, J.; Patel, B. B.; Patel, V.; Du, J.; Yu, Y.; Elliott, A. A.; Levi, E.; Sarkar, F. H. Curcumin Synergizes with Resveratrol to Inhibit Colon Cancer Nutr. Cancer 2009, 61 (4) 544-553 10.1080/01635580902752262
76. Caltagirone, S.; Rossi, C.; Poggi, A.; Ranelletti, F. O.; Natali, P. G.; Brunetti, M.; Aiello, F. B.; Piantelli, M. Flavonoids Apigenin and Quercetin Inhibit Melanoma Growth and Metastatic Potential Int. J. Cancer 2000, 87 (4) 595-600 10.1002/1097-0215(20000815)87:4<595::AID-IJC21>3.0.CO;2-5
77. Castellano, G.; González-Santander, J. L.; Lara, A.; Torrens, F. Classification of Flavonoid Compounds by Using Entropy of Information Theory Phytochemistry 2013, 93, 182-191 10.1016/j.phytochem.2013.03.024
78. Beekmann, K.; Actis-Goretta, L.; van Bladeren, P. J.; Dionisi, F.; Destaillats, F.; Rietjens, I. M. C. M. A State-of-the-Art Overview of the Effect of Metabolic Conjugation on the Biological Activity of Flavonoids Food Funct. 2012, 3 (10) 1008-1018 10.1039/c2fo30065f
79. Bors, W.; Heller, W.; Michel, C.; Saran, M. Flavonoids as Antioxidants: Determination of Radical-Scavenging Efficiencies Methods Enzymol. 1990, 186, 343-355 10.1016/0076-6879(90)86128-I
80. Croft, K. D. The Chemistry and Biological Effects of Flavonoids and Phenolic Acids Ann. N. Y. Acad. Sci. 1998, 854, 435-442 10.1111/j.1749-6632.1998.tb09922.x
81. Rasulev, B. F.; Abdullaev, N. D.; Syrov, V. N.; Leszczynski, J. A Quantitative Structure-Activity Relationship (QSAR) Study of the Antioxidant Activity of Flavonoids QSAR Comb. Sci. 2005, 24 (9) 1056-1065 10.1002/qsar.200430013
82. Rice-Evans, C. A.; Miller, N. J.; Paganga, G. Structure-Antioxidant Activity Relationships of Flavonoids and Phenolic Acids Free Radical Biol. Med. 1996, 20 (7) 933-956 10.1016/0891-5849(95)02227-9
83. Sakihama, Y.; Cohen, M. F.; Grace, S. C.; Yamasaki, H. Plant Phenolic Antioxidant and Prooxidant Activities: Phenolics-Induced Oxidative Damage Mediated by Metals in Plants Toxicology 2002, 177 (1) 67-80 10.1016/S0300-483X(02)00196-8
84. Khan, H. Y.; Zubair, H.; Ullah, M. F.; Ahmad, A.; Hadi, S. M. A Prooxidant Mechanism for the Anticancer and Chemopreventive Properties of Plant Polyphenols Curr. Drug Targets 2012, 13 (14) 1738-1749 10.2174/138945012804545560
85. Jørgensen, K. B. Photochemical Oxidative Cyclisation of Stilbenes and Stilbenoids - the Mallory-Reaction Molecules 2010, 15 (6) 4334-4358 10.3390/molecules15064334
86. Xiao, K.; Zhang, H.-J.; Xuan, L.-J.; Zhang, J.; Xu, Y.-M.; Bai, D.-L. Stilbenoids: Chemistry and Bioactivities. In Studies in Natural Products Chemistry; Bioactive Natural Products (Part N); Atta-ur-Rahman, Ed.; Elsevier: New York, 2008; Vol. 34, pp 453-646.
87. Stivala, L. A.; Savio, M.; Carafoli, F.; Perucca, P.; Bianchi, L.; Maga, G.; Forti, L.; Pagnoni, U. M.; Albini, A.; Prosperi, E.; Vannini, V. Specific Structural Determinants Are Responsible for the Antioxidant Activity and the Cell Cycle Effects of Resveratrol J. Biol. Chem. 2001, 276 (25) 22586-22594 10.1074/jbc.M101846200
88. Perecko, T.; Jancinova, V.; Drabikova, K.; Nosal, R.; Harmatha, J. Structure-Efficiency Relationship in Derivatives of Stilbene. Comparison of Resveratrol, Pinosylvin and Pterostilbene Neuro Endocrinol. Lett. 2008, 29 (5) 802-805
89. Kim, H.-S.; Quon, M. J.; Kim, J.-A. New Insights into the Mechanisms of Polyphenols beyond Antioxidant Properties; Lessons from the Green Tea Polyphenol, Epigallocatechin 3-Gallate Redox Biol. 2014, 2, 187-195 10.1016/j.redox.2013.12.022
90. Amić, D.; Davidović-Amić, D.; Beslo, D.; Rastija, V.; Lucić, B.; Trinajstić, N. SAR and QSAR of the Antioxidant Activity of Flavonoids Curr. Med. Chem. 2007, 14 (7) 827-845 10.2174/092986707780090954
91. Scalbert, A.; Manach, C.; Morand, C.; Rémésy, C.; Jiménez, L. Dietary Polyphenols and the Prevention of Diseases Crit. Rev. Food Sci. Nutr. 2005, 45 (4) 287-306 10.1080/1040869059096
92. Hollman, P. C. H. Unravelling of the Health Effects of Polyphenols Is a Complex Puzzle Complicated by Metabolism Arch. Biochem. Biophys. 2014, 559, 100-105 10.1016/j.abb.2014.04.013
93. Lopez, M. S.; Dempsey, R. J.; Vemuganti, R. Resveratrol Neuroprotection in Stroke and Traumatic CNS Injury Neurochem. Int. 2015, 89, 75-82 10.1016/j.neuint.2015.08.009
94. Costa, S. L.; Silva, V. D. A.; Dos Santos Souza, C.; Santos, C. C.; Paris, I.; Muñoz, P.; Segura-Aguilar, J. Impact of Plant-Derived Flavonoids on Neurodegenerative Diseases Neurotoxic. Res. 2016, 30 (1) 41-52 10.1007/s12640-016-9600-1
95. Kishimoto, Y.; Tani, M.; Kondo, K. Pleiotropic Preventive Effects of Dietary Polyphenols in Cardiovascular Diseases Eur. J. Clin. Nutr. 2013, 67 (5) 532-535 10.1038/ejcn.2013.29
96. Hügel, H. M.; Jackson, N.; May, B.; Zhang, A. L.; Xue, C. C. Polyphenol Protection and Treatment of Hypertension Phytomedicine 2016, 23 (2) 220-231 10.1016/j.phymed.2015.12.012
97. Escande, C.; Nin, V.; Price, N. L.; Capellini, V.; Gomes, A. P.; Barbosa, M. T.; O'Neil, L.; White, T. A.; Sinclair, D. A.; Chini, E. N. Flavonoid Apigenin Is an Inhibitor of the NAD+ Ase CD38: Implications for Cellular NAD+ Metabolism, Protein Acetylation, and Treatment of Metabolic Syndrome Diabetes 2013, 62 (4) 1084-1093 10.2337/db12-1139
98. Amiot, M. J.; Riva, C.; Vinet, A. Effects of Dietary Polyphenols on Metabolic Syndrome Features in Humans: A Systematic Review Obes. Rev. 2016, 17 (7) 573-586 10.1111/obr.12409
99. Storniolo, C. E.; Roselló-Catafau, J.; Pintó, X.; Mitjavila, M. T.; Moreno, J. J. Polyphenol Fraction of Extra Virgin Olive Oil Protects against Endothelial Dysfunction Induced by High Glucose and Free Fatty Acids through Modulation of Nitric Oxide and Endothelin-1 Redox Biol. 2014, 2, 971-977 10.1016/j.redox.2014.07.001
100. Rascón, B.; Hubbard, B. P.; Sinclair, D. A.; Amdam, G. V. The Lifespan Extension Effects of Resveratrol Are Conserved in the Honey Bee and May Be Driven by a Mechanism Related to Caloric Restriction Aging 2012, 4 (7) 499-508 10.18632/aging.100474
101. Lacroix, S.; Lauria, M.; Scott-Boyer, M.-P.; Marchetti, L.; Priami, C.; Caberlotto, L. Systems Biology Approaches to Study the Molecular Effects of Caloric Restriction and Polyphenols on Aging Processes Genes Nutr. 2015, 10, 58 10.1007/s12263-015-0508-9
102. Flowers, A.; Lee, J.-Y.; Acosta, S.; Hudson, C.; Small, B.; Sanberg, C. D.; Bickford, P. C.; Grimmig, B. NT-020 Treatment Reduces Inflammation and Augments Nrf-2 and Wnt Signaling in Aged Rats J. Neuroinflammation 2015, 12, 174 10.1186/s12974-015-0395-4
103. Bonaccio, M.; Pounis, G.; Cerletti, C.; Donati, M. B.; Iacoviello, L.; de Gaetano, G. Mediterranean Diet, Dietary Polyphenols and Low-Grade Inflammation: Results from the Moli-Sani Study Br. J. Clin. Pharmacol. 2017, 83 (1) 107-113 10.1111/bcp.12924
104. Sarkar, S.; Mazumder, S.; Saha, S. J.; Bandyopadhyay, U. Management of Inflammation by Natural Polyphenols: A Comprehensive Mechanistic Update Curr. Med. Chem. 2016, 23, 1657-1695 10.2174/0929867323666160418115540
105. Kang, N. J.; Shin, S. H.; Lee, H. J.; Lee, K. W. Polyphenols as Small Molecular Inhibitors of Signaling Cascades in Carcinogenesis Pharmacol. Ther. 2011, 130 (3) 310-324 10.1016/j.pharmthera.2011.02.004
106. Albini, A.; Tosetti, F.; Li, V. W.; Noonan, D. M.; Li, W. W. Cancer Prevention by Targeting Angiogenesis Nat. Rev. Clin. Oncol. 2012, 9 (9) 498-509 10.1038/nrclinonc.2012.120
107. Garg, A. K.; Buchholz, T. A.; Aggarwal, B. B. Chemosensitization and Radiosensitization of Tumors by Plant Polyphenols Antioxid. Redox Signaling 2005, 7 (11-12) 1630-1647 10.1089/ars.2005.7.1630
108. Chang, C.-M.; Chang, P.-Y.; Tu, M.-G.; Lu, C.-C.; Kuo, S.-C.; Amagaya, S.; Lee, C.-Y.; Jao, H.-Y.; Chen, M. Y.; Yang, J.-S. Epigallocatechin Gallate Sensitizes CAL-27 Human Oral Squamous Cell Carcinoma Cells to the Anti-Metastatic Effects of Gefitinib (Iressa) via Synergistic Suppression of Epidermal Growth Factor Receptor and Matrix Metalloproteinase-2 Oncol. Rep. 2012, 28 (5) 1799-1807 10.3892/or.2012.1991
109. Nair, S.; Li, W.; Kong, A.-N. T. Natural Dietary Anti-Cancer Chemopreventive Compounds: Redox-Mediated Differential Signaling Mechanisms in Cytoprotection of Normal Cells versus Cytotoxicity in Tumor Cells Acta Pharmacol. Sin. 2007, 28 (4) 459-472 10.1111/j.1745-7254.2007.00549.x
110. Hanahan, D.; Weinberg, R. A. Hallmarks of Cancer: The next Generation Cell 2011, 144 (5) 646-674 10.1016/j.cell.2011.02.013
111. Yu, R.; Hebbar, V.; Kim, D. W.; Mandlekar, S.; Pezzuto, J. M.; Kong, A. N. Resveratrol Inhibits Phorbol Ester and UV-Induced Activator Protein 1 Activation by Interfering with Mitogen-Activated Protein Kinase Pathways Mol. Pharmacol. 2001, 60 (1) 217-224 10.1124/mol.60.1.217
112. Banerjee, N.; Kim, H.; Talcott, S. T.; Turner, N. D.; Byrne, D. H.; Mertens-Talcott, S. U. Plum Polyphenols Inhibit Colorectal Aberrant Crypt Foci Formation in Rats: Potential Role of the miR-143/protein Kinase B/mammalian Target of Rapamycin Axis Nutr. Res. 2016, 36 (10) 1105-1113 10.1016/j.nutres.2016.06.008
113. Pandima Devi, K.; Rajavel, T.; Daglia, M.; Nabavi, S. F.; Bishayee, A.; Nabavi, S. M. Targeting miRNAs by Polyphenols: Novel Therapeutic Strategy for Cancer. Semin. Cancer Biol. 2017, 10.1016/j.semcancer.2017.02.001, in press.
114. Dou, Q. P. Molecular Mechanisms of Green Tea Polyphenols Nutr. Cancer 2009, 61 (6) 827-835 10.1080/01635580903285049
115. Zhou, H.; Beevers, C. S.; Huang, S. The Targets of Curcumin Curr. Drug Targets 2011, 12 (3) 332-347 10.2174/138945011794815356
116. Buhrmann, C.; Shayan, P.; Kraehe, P.; Popper, B.; Goel, A.; Shakibaei, M. Resveratrol Induces Chemosensitization to 5-Fluorouracil through up-Regulation of Intercellular Junctions, Epithelial-to-Mesenchymal Transition and Apoptosis in Colorectal Cancer Biochem. Pharmacol. 2015, 98 (1) 51-68 10.1016/j.bcp.2015.08.105
117. Mena, S.; Rodríguez, M. L.; Ponsoda, X.; Estrela, J. M.; Jäättela, M.; Ortega, A. L. Pterostilbene-Induced Tumor Cytotoxicity: A Lysosomal Membrane Permeabilization-Dependent Mechanism PLoS One 2012, 7 (9) e44524 10.1371/journal.pone.0044524
118. Saadatdoust, Z.; Pandurangan, A. K.; Ananda Sadagopan, S. K.; Esa, N. M.; Ismail, A.; Mustafa, M. R. Dietary Cocoa Inhibits Colitis Associated Cancer: A Crucial Involvement of the IL-6/STAT3 Pathway J. Nutr. Biochem. 2015, 26 (12) 1547-1558 10.1016/j.jnutbio.2015.07.024
119. Quoc Trung, L.; Espinoza, J. L.; Takami, A.; Nakao, S. Resveratrol Induces Cell Cycle Arrest and Apoptosis in Malignant NK Cells via JAK2/STAT3 Pathway Inhibition PLoS One 2013, 8 (1) e55183 10.1371/journal.pone.0055183
120. Semwal, D. K.; Semwal, R. B.; Combrinck, S.; Viljoen, A. Myricetin: A Dietary Molecule with Diverse Biological Activities Nutrients 2016, 8 (2) 90 10.3390/nu8020090
121. Meeran, S. M.; Katiyar, S. K. Cell Cycle Control as a Basis for Cancer Chemoprevention through Dietary Agents Front. Biosci., Landmark Ed. 2008, 13, 2191-2202 10.2741/2834
122. ATCC: The Global Bioresource Center; ATCC, LGC Standards: Teddington, Middlesex, UK, 2016; https://www.lgcstandards-atcc.org/?geo-country=es (accessed Nov 7, 2016).
123. Cui, J.; Yu, B.; Zhao, Y.; Zhu, W.; Li, H.; Lou, H.; Zhai, G. Enhancement of Oral Absorption of Curcumin by Self-Microemulsifying Drug Delivery Systems Int. J. Pharm. 2009, 371 (1-2) 148-155 10.1016/j.ijpharm.2008.12.009
124. Asensi, M.; Medina, I.; Ortega, A.; Carretero, J.; Baño, M. C.; Obrador, E.; Estrela, J. M. Inhibition of Cancer Growth by Resveratrol Is Related to Its Low Bioavailability Free Radical Biol. Med. 2002, 33 (3) 387-398 10.1016/S0891-5849(02)00911-5
125. Lambert, J. D.; Lee, M.-J.; Lu, H.; Meng, X.; Hong, J. J. J.; Seril, D. N.; Sturgill, M. G.; Yang, C. S. Epigallocatechin-3-Gallate Is Absorbed but Extensively Glucuronidated Following Oral Administration to Mice J. Nutr. 2003, 133 (12) 4172-4177
126. Zhongfa, L.; Chiu, M.; Wang, J.; Chen, W.; Yen, W.; Fan-Havard, P.; Yee, L. D.; Chan, K. K. Enhancement of Curcumin Oral Absorption and Pharmacokinetics of Curcuminoids and Curcumin Metabolites in Mice Cancer Chemother. Pharmacol. 2012, 69 (3) 679-689 10.1007/s00280-011-1749-y
127. Ju, Y. H.; Doerge, D. R.; Woodling, K. A.; Hartman, J. A.; Kwak, J.; Helferich, W. G. Dietary Genistein Negates the Inhibitory Effect of Letrozole on the Growth of Aromatase-Expressing Estrogen-Dependent Human Breast Cancer Cells (MCF-7Ca) in Vivo Carcinogenesis 2008, 29 (11) 2162-2168 10.1093/carcin/bgn161
128. Baell, J. B.; Holloway, G. A. New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays J. Med. Chem. 2010, 53 (7) 2719-2740 10.1021/jm901137j
129. Baell, J.; Walters, M. A. Chemistry: Chemical Con Artists Foil Drug Discovery Nature 2014, 513 (7519) 481-483 10.1038/513481a
130. Priyadarsini, K. I. Chemical and Structural Features Influencing the Biological Activity of Curcumin Curr. Pharm. Des. 2013, 19 (11) 2093-2100 10.2174/1381612811319110010
131. Ingólfsson, H. I.; Thakur, P.; Herold, K. F.; Hobart, E. A.; Ramsey, N. B.; Periole, X.; de Jong, D. H.; Zwama, M.; Yilmaz, D.; Hall, K.; Maretzky, T.; Hemmings, H. C.; Blobel, C.; Marrink, S. J.; Koçer, A.; Sack, J. T.; Andersen, O. S. Phytochemicals Perturb Membranes and Promiscuously Alter Protein Function ACS Chem. Biol. 2014, 9 (8) 1788-1798 10.1021/cb500086e
132. Bruggisser, R.; von Daeniken, K.; Jundt, G.; Schaffner, W.; Tullberg-Reinert, H. Interference of Plant Extracts, Phytoestrogens and Antioxidants with the MTT Tetrazolium Assay Planta Med. 2002, 68 (5) 445-448 10.1055/s-2002-32073
133. Bravo, L. Polyphenols: Chemistry, Dietary Sources, Metabolism, and Nutritional Significance Nutr. Rev. 1998, 56 (11) 317-333 10.1111/j.1753-4887.1998.tb01670.x
134. Ozdal, T.; Sela, D. A.; Xiao, J.; Boyacioglu, D.; Chen, F.; Capanoglu, E. The Reciprocal Interactions between Polyphenols and Gut Microbiota and Effects on Bioaccessibility Nutrients 2016, 8 (2) 78 10.3390/nu8020078
135. Dai, P.; Zhu, L.; Luo, F.; Lu, L.; Li, Q.; Wang, L.; Wang, Y.; Wang, X.; Hu, M.; Liu, Z. Triple Recycling Processes Impact Systemic and Local Bioavailability of Orally Administered Flavonoids AAPS J. 2015, 17 (3) 723-736 10.1208/s12248-015-9732-x
136. Clinical Trials Information for Patients and Caregivers; National Cancer Institute: Bethesda, MD, 2016; http://www.cancer.gov/about-cancer/treatment/clinical-trials (accessed Jul 28, 2016).
137. Yu, W.; Fu, Y.-C.; Wang, W. Cellular and Molecular Effects of Resveratrol in Health and Disease J. Cell. Biochem. 2012, 113 (3) 752-759 10.1002/jcb.23431
138. Jang, M.; Cai, L.; Udeani, G. O.; Slowing, K. V.; Thomas, C. F.; Beecher, C. W.; Fong, H. H. S.; Farnsworth, N. R.; Kinghorn, A. D.; Mehta, R. G.; Moon, R. C.; Pezzuto, J. M. Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes Science 1997, 275 (5297) 218-220 10.1126/science.275.5297.218
139. Ndiaye, M.; Philippe, C.; Mukhtar, H.; Ahmad, N. The Grape Antioxidant Resveratrol for Skin Disorders: Promise, Prospects, and Challenges Arch. Biochem. Biophys. 2011, 508 (2) 164-170 10.1016/j.abb.2010.12.030
140. Roupe, K. A.; Remsberg, C. M.; Yáñez, J. A.; Davies, N. M. Pharmacometrics of Stilbenes: Seguing towards the Clinic Curr. Clin. Pharmacol. 2006, 1 (1) 81-101 10.2174/157488406775268246
141. Cottart, C.-H.; Nivet-Antoine, V.; Laguillier-Morizot, C.; Beaudeux, J.-L. Resveratrol Bioavailability and Toxicity in Humans Mol. Nutr. Food Res. 2010, 54 (1) 7-16 10.1002/mnfr.200900437
142. Dellinger, R. W.; Gomez Garcia, A. M.; Meyskens, F. L. Differences in the Glucuronidation of Resveratrol and Pterostilbene: Altered Enzyme Specificity and Potential Gender Differences Drug Metab. Pharmacokinet. 2014, 29 (2) 112-119 10.2133/dmpk.DMPK-13-RG-012
143. Oda, S.; Fukami, T.; Yokoi, T.; Nakajima, M. A Comprehensive Review of UDP-Glucuronosyltransferase and Esterases for Drug Development Drug Metab. Pharmacokinet. 2015, 30 (1) 30-51 10.1016/j.dmpk.2014.12.001
144. Gambini, J.; Inglés, M.; Olaso, G.; Lopez-Grueso, R.; Bonet-Costa, V.; Gimeno-Mallench, L.; Mas-Bargues, C.; Abdelaziz, K. M.; Gomez-Cabrera, M. C.; Vina, J.; Borras, C. Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans Oxid. Med. Cell. Longevity 2015, 2015, 837042 10.1155/2015/837042
145. Novelle, M. G.; Wahl, D.; Diéguez, C.; Bernier, M.; de Cabo, R. Resveratrol Supplementation: Where Are We Now and Where Should We Go? Ageing Res. Rev. 2015, 21, 1-15 10.1016/j.arr.2015.01.002
146. Das, S.; Ng, K.-Y. Colon-Specific Delivery of Resveratrol: Optimization of Multi-Particulate Calcium-Pectinate Carrier Int. J. Pharm. 2010, 385 (1-2) 20-28 10.1016/j.ijpharm.2009.10.016
147. Kim, S. H.; Adhikari, B. B.; Cruz, S.; Schramm, M. P.; Vinson, J. A.; Narayanaswami, V. Targeted Intracellular Delivery of Resveratrol to Glioblastoma Cells Using Apolipoprotein E-Containing Reconstituted HDL as a Nanovehicle PLoS One 2015, 10 (8) e0135130 10.1371/journal.pone.0135130
148. Pan, M.-H.; Chiou, Y.-S.; Chen, W.-J.; Wang, J.-M.; Badmaev, V.; Ho, C.-T. Pterostilbene Inhibited Tumor Invasion via Suppressing Multiple Signal Transduction Pathways in Human Hepatocellular Carcinoma Cells Carcinogenesis 2009, 30 (7) 1234-1242 10.1093/carcin/bgp121
149. Estrela, J. M.; Ortega, A.; Mena, S.; Rodriguez, M. L.; Asensi, M. Pterostilbene: Biomedical Applications Crit. Rev. Clin. Lab. Sci. 2013, 50 (3) 65-78 10.3109/10408363.2013.805182
150. Riche, D. M.; McEwen, C. L.; Riche, K. D.; Sherman, J. J.; Wofford, M. R.; Deschamp, D.; Griswold, M. Analysis of Safety from a Human Clinical Trial with Pterostilbene J. Toxicol. 2013, 2013, 463595 10.1155/2013/463595
151. Riche, D. M.; Riche, K. D.; Blackshear, C. T.; McEwen, C. L.; Sherman, J. J.; Wofford, M. R.; Griswold, M. E. Pterostilbene on Metabolic Parameters: A Randomized, Double-Blind, and Placebo-Controlled Trial Evid.-Based Complement. Altern. Med. 2014, 2014, 459165 10.1155/2014/459165
152. Spagnuolo, C.; Russo, G. L.; Orhan, I. E.; Habtemariam, S.; Daglia, M.; Sureda, A.; Nabavi, S. F.; Devi, K. P.; Loizzo, M. R.; Tundis, R.; Nabavi, S. M. Genistein and Cancer: Current Status, Challenges, and Future Directions Adv. Nutr. 2015, 6 (4) 408-419 10.3945/an.114.008052
153. Peng, B.; Cao, J.; Yi, S.; Wang, C.; Zheng, G.; He, Z. Inhibition of Proliferation and Induction of G1-Phase Cell-Cycle Arrest by dFMGEN, a Novel Genistein Derivative, in Lung Carcinoma A549 Cells Drug Chem. Toxicol. 2013, 36 (2) 196-204 10.3109/01480545.2012.710620
154. Caëtano, B.; Le Corre, L.; Chalabi, N.; Delort, L.; Bignon, Y.-J.; Bernard-Gallon, D. J. Soya Phytonutrients Act on a Panel of Genes Implicated with BRCA1 and BRCA2 Oncosuppressors in Human Breast Cell Lines Br. J. Nutr. 2006, 95 (2) 406-413 10.1079/BJN20051640
155. Liu, B.; Edgerton, S.; Yang, X.; Kim, A.; Ordonez-Ercan, D.; Mason, T.; Alvarez, K.; McKimmey, C.; Liu, N.; Thor, A. Low-Dose Dietary Phytoestrogen Abrogates Tamoxifen-Associated Mammary Tumor Prevention Cancer Res. 2005, 65 (3) 879-886
156. Seo, H.-S.; DeNardo, D. G.; Jacquot, Y.; Laïos, I.; Vidal, D. S.; Zambrana, C. R.; Leclercq, G.; Brown, P. H. Stimulatory Effect of Genistein and Apigenin on the Growth of Breast Cancer Cells Correlates with Their Ability to Activate ER Alpha Breast Cancer Res. Treat. 2006, 99 (2) 121-134 10.1007/s10549-006-9191-2
157. Hirose, M.; Takesada, Y.; Tanaka, H.; Tamano, S.; Kato, T.; Shirai, T. Carcinogenicity of Antioxidants BHA, Caffeic Acid, Sesamol, 4-Methoxyphenol and Catechol at Low Doses, Either Alone or in Combination, and Modulation of Their Effects in a Rat Medium-Term Multi-Organ Carcinogenesis Model Carcinogenesis 1998, 19 (1) 207-212 10.1093/carcin/19.1.207
158. Hirose, M.; Hoshiya, T.; Mizoguchi, Y.; Nakamura, A.; Akagi, K.; Shirai, T. Green Tea Catechins Enhance Tumor Development in the Colon without Effects in the Lung or Thyroid after Pretreatment with 1,2-Dimethylhydrazine or 2,2'-dihydroxy-Di-N-Propylnitrosamine in Male F344 Rats Cancer Lett. 2001, 168 (1) 23-29 10.1016/S0304-3835(01)00502-X
159. Zhu, B. T.; Liehr, J. G. Quercetin Increases the Severity of Estradiol-Induced Tumorigenesis in Hamster Kidney Toxicol. Appl. Pharmacol. 1994, 125 (1) 149-158 10.1006/taap.1994.1059
160. Ameer, B.; Weintraub, R. A. Drug Interactions with Grapefruit Juice Clin. Pharmacokinet. 1997, 33 (2) 103-121 10.2165/00003088-199733020-00003
161. Harwood, M.; Danielewska-Nikiel, B.; Borzelleca, J. F.; Flamm, G. W.; Williams, G. M.; Lines, T. C. A Critical Review of the Data Related to the Safety of Quercetin and Lack of Evidence of in Vivo Toxicity, Including Lack of Genotoxic/carcinogenic Properties Food Chem. Toxicol. 2007, 45 (11) 2179-2205 10.1016/j.fct.2007.05.015
162. Gugler, R.; Leschik, M.; Dengler, H. J. Disposition of Quercetin in Man after Single Oral and Intravenous Doses Eur. J. Clin. Pharmacol. 1975, 9 (2-3) 229-234 10.1007/BF00614022
163. Ferry, D. R.; Smith, A.; Malkhandi, J.; Fyfe, D. W.; deTakats, P. G.; Anderson, D.; Baker, J.; Kerr, D. J. Phase I Clinical Trial of the Flavonoid Quercetin: Pharmacokinetics and Evidence for in Vivo Tyrosine Kinase Inhibition Clin. Cancer Res. 1996, 2 (4) 659-668
164. Murakami, A. Dose-Dependent Functionality and Toxicity of Green Tea Polyphenols in Experimental Rodents Arch. Biochem. Biophys. 2014, 557, 3-10 10.1016/j.abb.2014.04.018
165. Lambert, J. D.; Sang, S.; Yang, C. S. Possible Controversy over Dietary Polyphenols: Benefits vs Risks Chem. Res. Toxicol. 2007, 20 (4) 583-585 10.1021/tx7000515
166. Edwards, J. A.; Beck, M.; Riegger, C.; Bausch, J. Safety of Resveratrol with Examples for High Purity, Trans-Resveratrol, resVida(®) Ann. N. Y. Acad. Sci. 2011, 1215, 131-137 10.1111/j.1749-6632.2010.05855.x
167. Hebbar, V.; Shen, G.; Hu, R.; Kim, B.-R.; Chen, C.; Korytko, P. J.; Crowell, J. A.; Levine, B. S.; Kong, A.-N. T. Toxicogenomics of Resveratrol in Rat Liver Life Sci. 2005, 76 (20) 2299-2314 10.1016/j.lfs.2004.10.039
168. Priego, S.; Feddi, F.; Ferrer, P.; Mena, S.; Benlloch, M.; Ortega, A.; Carretero, J.; Obrador, E.; Asensi, M.; Estrela, J. M. Natural Polyphenols Facilitate Elimination of HT-29 Colorectal Cancer Xenografts by Chemoradiotherapy: A Bcl-2- and Superoxide Dismutase 2-Dependent Mechanism Mol. Cancer Ther. 2008, 7 (10) 3330-3342 10.1158/1535-7163.MCT-08-0363
169. Le Gal, K.; Ibrahim, M. X.; Wiel, C.; Sayin, V. I.; Akula, M. K.; Karlsson, C.; Dalin, M. G.; Akyürek, L. M.; Lindahl, P.; Nilsson, J.; Bergo, M. O. Antioxidants Can Increase Melanoma Metastasis in Mice Sci. Transl. Med. 2015, 7 (308) 308re8 10.1126/scitranslmed.aad3740
170. Obrador, E.; Benlloch, M.; Pellicer, J. A.; Asensi, M.; Estrela, J. M. Intertissue Flow of Glutathione (GSH) as a Tumor Growth-Promoting Mechanism: Interleukin 6 Induces GSH Release from Hepatocytes in Metastatic B16 Melanoma-Bearing Mice J. Biol. Chem. 2011, 286 (18) 15716-15727 10.1074/jbc.M110.196261
171. Estrela, J. M.; Ortega, A.; Mena, S.; Sirerol, J. A.; Obrador, E. Glutathione in Metastases: From Mechanisms to Clinical Applications Crit. Rev. Clin. Lab. Sci. 2016, 53 (4) 253-267 10.3109/10408363.2015.1136259
172. Garrett, W. S. Cancer and the Microbiota Science 2015, 348 (6230) 80-86 10.1126/science.aaa4972
173. Duda-Chodak, A.; Tarko, T.; Satora, P.; Sroka, P. Interaction of Dietary Compounds, Especially Polyphenols, with the Intestinal Microbiota: A Review Eur. J. Nutr. 2015, 54 (3) 325-341 10.1007/s00394-015-0852-y
174. Lee, H. C.; Jenner, A. M.; Low, C. S.; Lee, Y. K. Effect of Tea Phenolics and Their Aromatic Fecal Bacterial Metabolites on Intestinal Microbiota Res. Microbiol. 2006, 157 (9) 876-884 10.1016/j.resmic.2006.07.004
175. Caddeo, C.; Nacher, A.; Vassallo, A.; Armentano, M. F.; Pons, R.; Fernàndez-Busquets, X.; Carbone, C.; Valenti, D.; Fadda, A. M.; Manconi, M. Effect of Quercetin and Resveratrol Co-Incorporated in Liposomes against Inflammatory/oxidative Response Associated with Skin Cancer Int. J. Pharm. 2016, 513 (1-2) 153-163 10.1016/j.ijpharm.2016.09.014
176. Li, W.; Ma, J.; Ma, Q.; Li, B.; Han, L.; Liu, J.; Xu, Q.; Duan, W.; Yu, S.; Wang, F.; Wu, E. Resveratrol Inhibits the Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells via Suppression of the PI-3K/Akt/NF-κB Pathway Curr. Med. Chem. 2013, 20 (33) 4185-4194 10.2174/09298673113209990251
177. Pan, C.; Hu, Y.; Li, J.; Wang, Z.; Huang, J.; Zhang, S.; Ding, L. Estrogen Receptor-α36 Is Involved in Pterostilbene-Induced Apoptosis and Anti-Proliferation in in Vitro and in Vivo Breast Cancer PLoS One 2014, 9 (8) e104459 10.1371/journal.pone.0104459
178. Cheng, T.-C.; Lai, C.-S.; Chung, M.-C.; Kalyanam, N.; Majeed, M.; Ho, C.-T.; Ho, Y.-S.; Pan, M.-H. Potent Anti-Cancer Effect of 3′-hydroxypterostilbene in Human Colon Xenograft Tumors PLoS One 2014, 9 (11) e111814 10.1371/journal.pone.0111814
179. Kennedy, D. O. Polyphenols and the Human Brain: Plant "secondary Metabolite" Ecologic Roles and Endogenous Signaling Functions Drive Benefits Adv. Nutr. 2014, 5 (5) 515-533 10.3945/an.114.006320
180. Obrador, E.; Valles, S. L.; Benlloch, M.; Sirerol, J. A.; Pellicer, J. A.; Alcácer, J.; Coronado, J. A.-F.; Estrela, J. M. Glucocorticoid Receptor Knockdown Decreases the Antioxidant Protection of B16 Melanoma Cells: An Endocrine System-Related Mechanism That Compromises Metastatic Cell Resistance to Vascular Endothelium-Induced Tumor Cytotoxicity PLoS One 2014, 9 (5) e96466 10.1371/journal.pone.0096466
181. Valles, S. L.; Benlloch, M.; Rodriguez, M. L.; Mena, S.; Pellicer, J. A.; Asensi, M.; Obrador, E.; Estrela, J. M. Stress Hormones Promote Growth of B16-F10 Melanoma Metastases: An Interleukin 6- and Glutathione-Dependent Mechanism J. Transl. Med. 2013, 11, 72 10.1186/1479-5876-11-72
182. Schlossmacher, G.; Stevens, A.; White, A. Glucocorticoid Receptor-Mediated Apoptosis: Mechanisms of Resistance in Cancer Cells J. Endocrinol. 2011, 211 (1) 17-25 10.1530/JOE-11-0135
183. Volden, P. A.; Conzen, S. D. The Influence of Glucocorticoid Signaling on Tumor Progression Brain, Behav., Immun. 2013, 30 (Suppl) S26-S31 10.1016/j.bbi.2012.10.022
184. Hasegawa, E.; Nakagawa, S.; Sato, M.; Tachikawa, E.; Yamato, S. Effect of Polyphenols on Production of Steroid Hormones from Human Adrenocortical NCI-H295R Cells Biol. Pharm. Bull. 2013, 36 (2) 228-237 10.1248/bpb.b12-00627
185. Panickar, K. S. Effects of Dietary Polyphenols on Neuroregulatory Factors and Pathways That Mediate Food Intake and Energy Regulation in Obesity Mol. Nutr. Food Res. 2013, 57 (1) 34-47 10.1002/mnfr.201200431
186. Garofalo, C.; Surmacz, E. Leptin and Cancer J. Cell. Physiol. 2006, 207 (1) 12-22 10.1002/jcp.20472
187. Sirotkin, A. V.; Harrath, A. H. Phytoestrogens and Their Effects Eur. J. Pharmacol. 2014, 741, 230-236 10.1016/j.ejphar.2014.07.057
188. Pihlajamaa, P.; Zhang, F.-P.; Saarinen, L.; Mikkonen, L.; Hautaniemi, S.; Jänne, O. A. The Phytoestrogen Genistein Is a Tissue-Specific Androgen Receptor Modulator Endocrinology 2011, 152 (11) 4395-4405 10.1210/en.2011-0221
189. He, J.; Wang, S.; Zhou, M.; Yu, W.; Zhang, Y.; He, X. Phytoestrogens and Risk of Prostate Cancer: A Meta-Analysis of Observational Studies World J. Surg. Oncol. 2015, 13, 231 10.1186/s12957-015-0648-9
190. Bilal, I.; Chowdhury, A.; Davidson, J.; Whitehead, S. Phytoestrogens and Prevention of Breast Cancer: The Contentious Debate World J. Clin. Oncol. 2014, 5 (4) 705-712 10.5306/wjco.v5.i4.705
191. Albini, A.; Rosano, C.; Angelini, G.; Amaro, A.; Esposito, A. I.; Maramotti, S.; Noonan, D. M.; Pfeffer, U. Exogenous Hormonal Regulation in Breast Cancer Cells by Phytoestrogens and Endocrine Disruptors Curr. Med. Chem. 2014, 21 (9) 1129-1145 10.2174/0929867321666131129124640
192. de Lemos, M. L. Effects of Soy Phytoestrogens Genistein and Daidzein on Breast Cancer Growth Ann. Pharmacother. 2001, 35 (9) 1118-1121 10.1345/aph.10257
193. Yang, X.; Belosay, A.; Hartman, J. A.; Song, H.; Zhang, Y.; Wang, W.; Doerge, D. R.; Helferich, W. G. Dietary Soy Isoflavones Increase Metastasis to Lungs in an Experimental Model of Breast Cancer with Bone Micro-Tumors Clin. Exp. Metastasis 2015, 32 (4) 323-333 10.1007/s10585-015-9709-2
194. Trifunović, S.; Manojlović-Stojanoski, M.; Ajdzanović, V.; Nestorović, N.; Ristić, N.; Medigović, I.; Milošević, V. Genistein Stimulates the Hypothalamo-Pituitary-Adrenal Axis in Adult Rats: Morphological and Hormonal Study Histol. Histopathol. 2012, 27 (5) 627-640 10.14670/HH-27.627
195. Ajdzanovic, V. Z.; Sosi-Jurjevic, B. T.; Filipóvic, B. R.; Trifunovic, S. L.; Brkic, D. D.; Sekulic, M. I.; Milosevic, V. L. Genistein Affects the Morphology of Pituitary ACTH Cells and Decreases Circulating Levels of ACTH and Corticosterone in Middle-Aged Male Rats Biol. Res. 2009, 42 (1) 13-23 10.4067/S0716-97602009000100002
196. Hong, J.; Lu, H.; Meng, X.; Ryu, J.-H.; Hara, Y.; Yang, C. S. Stability, Cellular Uptake, Biotransformation, and Efflux of Tea Polyphenol (-)-Epigallocatechin-3-gallate in HT-29 Human Colon Adenocarcinoma Cells Cancer Res. 2002, 62 (24) 7241-7246
197. Han, Y.-S.; Bastianetto, S.; Dumont, Y.; Quirion, R. Specific Plasma Membrane Binding Sites for Polyphenols, Including Resveratrol, in the Rat Brain J. Pharmacol. Exp. Ther. 2006, 318 (1) 238-245 10.1124/jpet.106.102319
198. Tachibana, H. Green Tea Polyphenol Sensing Proc. Jpn. Acad., Ser. B 2011, 87 (3) 66-80 10.2183/pjab.87.66
199. Micucci, C.; Valli, D.; Matacchione, G.; Catalano, A. Current Perspectives between Metabolic Syndrome and Cancer Oncotarget 2016, 7 (25) 38959-38972 10.18632/oncotarget.8341
200. EL Andaloussi, S.; Mäger, I.; Breakefield, X. O.; Wood, M. J. A. Extracellular Vesicles: Biology and Emerging Therapeutic Opportunities Nat. Rev. Drug Discovery 2013, 12 (5) 347-357 10.1038/nrd3978
201. Jang, J.-Y.; Lee, J.-K.; Jeon, Y.-K.; Kim, C.-W. Exosome Derived from Epigallocatechin Gallate Treated Breast Cancer Cells Suppresses Tumor Growth by Inhibiting Tumor-Associated Macrophage Infiltration and M2 Polarization BMC Cancer 2013, 13, 421 10.1186/1471-2407-13-421
202. Osterman, C. J. D.; Lynch, J. C.; Leaf, P.; Gonda, A.; Ferguson Bennit, H. R.; Griffiths, D.; Wall, N. R. Curcumin Modulates Pancreatic Adenocarcinoma Cell-Derived Exosomal Function PLoS One 2015, 10 (7) e0132845 10.1371/journal.pone.0132845
203. Williamson, M. P.; McCormick, T. G.; Nance, C. L.; Shearer, W. T. Epigallocatechin Gallate, the Main Polyphenol in Green Tea, Binds to the T-Cell Receptor, CD4: Potential for HIV-1 Therapy J. Allergy Clin. Immunol. 2006, 118 (6) 1369-1374 10.1016/j.jaci.2006.08.016
204. Kueny-Stotz, M.; Chassaing, S.; Brouillard, R.; Nielsen, M.; Goeldner, M. Flavylium Salts as in Vitro Precursors of Potent Ligands to Brain GABA-A Receptors Bioorg. Med. Chem. Lett. 2008, 18 (17) 4864-4867 10.1016/j.bmcl.2008.07.107
205. Siddiqui, I. A.; Asim, M.; Hafeez, B. B.; Adhami, V. M.; Tarapore, R. S.; Mukhtar, H. Green Tea Polyphenol EGCG Blunts Androgen Receptor Function in Prostate Cancer FASEB J. 2011, 25 (4) 1198-1207 10.1096/fj.10-167924
206. Mohammadi-Bardbori, A.; Bengtsson, J.; Rannug, U.; Rannug, A.; Wincent, E. Quercetin, Resveratrol, and Curcumin Are Indirect Activators of the Aryl Hydrocarbon Receptor (AHR) Chem. Res. Toxicol. 2012, 25 (9) 1878-1884 10.1021/tx300169e
207. Shay, J.; Elbaz, H. A.; Lee, I.; Zielske, S. P.; Malek, M. H.; Hüttemann, M. Molecular Mechanisms and Therapeutic Effects of (-)-Epicatechin and Other Polyphenols in Cancer, Inflammation, Diabetes, and Neurodegeneration Oxid. Med. Cell. Longevity 2015, 2015, 181260 10.1155/2015/181260
208. Seely, K. A.; Levi, M. S.; Prather, P. L. The Dietary Polyphenols Trans-Resveratrol and Curcumin Selectively Bind Human CB1 Cannabinoid Receptors with Nanomolar Affinities and Function as Antagonists/inverse Agonists J. Pharmacol. Exp. Ther. 2009, 330 (1) 31-39 10.1124/jpet.109.151654
209. Korte, G.; Dreiseitel, A.; Schreier, P.; Oehme, A.; Locher, S.; Geiger, S.; Heilmann, J.; Sand, P. G. Tea Catechins' Affinity for Human Cannabinoid Receptors Phytomedicine 2010, 17 (1) 19-22 10.1016/j.phymed.2009.10.001
210. Velasco, G.; Sánchez, C.; Guzmán, M. Anticancer Mechanisms of Cannabinoids Curr. Oncol. Tor. Ont 2016, 23 (2) S23-S32 10.3747/co.23.3080
211. Ohara, M.; Ohyama, Y. Delivery and Application of Dietary Polyphenols to Target Organs, Tissues and Intracellular Organelles Curr. Drug Metab. 2014, 15 (1) 37-47 10.2174/1389200214666131210143407
212. Halake, K.; Birajdar, M.; Lee, J. Structural Implications of Polyphenolic Antioxidants J. Ind. Eng. Chem. 2016, 35, 1-7 10.1016/j.jiec.2016.01.003
213. Rimando, A. M.; Cuendet, M.; Desmarchelier, C.; Mehta, R. G.; Pezzuto, J. M.; Duke, S. O. Cancer Chemopreventive and Antioxidant Activities of Pterostilbene, a Naturally Occurring Analogue of Resveratrol J. Agric. Food Chem. 2002, 50 (12) 3453-3457 10.1021/jf0116855
214. Siddiqui, A.; Dandawate, P.; Rub, R.; Padhye, S.; Aphale, S.; Moghe, A.; Jagyasi, A.; Venkateswara Swamy, K.; Singh, B.; Chatterjee, A.; Ronghe, A.; Bhat, H. K. Novel Aza-Resveratrol Analogs: Synthesis, Characterization and Anticancer Activity against Breast Cancer Cell Lines Bioorg. Med. Chem. Lett. 2013, 23 (3) 635-640 10.1016/j.bmcl.2012.12.002
215. Landis-Piwowar, K. R.; Huo, C.; Chen, D.; Milacic, V.; Shi, G.; Chan, T. H.; Dou, Q. P. A Novel Prodrug of the Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate as a Potential Anticancer Agent Cancer Res. 2007, 67 (9) 4303-4310 10.1158/0008-5472.CAN-06-4699
216. Yu, Z.; Qin, X. L.; Gu, Y. Y.; Chen, D.; Cui, Q. C.; Jiang, T.; Wan, S. B.; Dou, Q. P. Prodrugs of Fluoro-Substituted Benzoates of EGC as Tumor Cellular Proteasome Inhibitors and Apoptosis Inducers Int. J. Mol. Sci. 2008, 9 (6) 951-961 10.3390/ijms9060951
217. Sánchez-del-Campo, L.; Otón, F.; Tárraga, A.; Cabezas-Herrera, J.; Chazarra, S.; Rodríguez-López, J. N. Synthesis and Biological Activity of a 3,4,5-Trimethoxybenzoyl Ester Analogue of Epicatechin-3-Gallate J. Med. Chem. 2008, 51 (7) 2018-2026 10.1021/jm701346h
218. Biasutto, L.; Zoratti, M. Prodrugs of Quercetin and Resveratrol: A Strategy under Development Curr. Drug Metab. 2014, 15 (1) 77-95 10.2174/1389200214666131211160005
219. Shaikh, J.; Ankola, D. D.; Beniwal, V.; Singh, D.; Kumar, M. N. V. R. Nanoparticle Encapsulation Improves Oral Bioavailability of Curcumin by at Least 9-Fold When Compared to Curcumin Administered with Piperine as Absorption Enhancer Eur. J. Pharm. Sci. 2009, 37 (3-4) 223-230 10.1016/j.ejps.2009.02.019
220. Bansal, S. S.; Goel, M.; Aqil, F.; Vadhanam, M. V.; Gupta, R. C. Advanced Drug Delivery Systems of Curcumin for Cancer Chemoprevention Cancer Prev. Res. 2011, 4 (8) 1158-1171 10.1158/1940-6207.CAPR-10-0006
221. Volkheimer, G.; Schulz, F. H.; Lehmann, H.; Aurich, I.; Hübner, R.; Hübner, M.; Hallmayer, A.; Münch, H.; Oppermann, H.; Strauch, S. Primary Portal Transport of Persorbed Starch Granules from the Intestinal Wall Pharmacology 2004, 18 (2) 103-108 10.1159/000137143
222. Sarin, H.; Kanevsky, A. S.; Wu, H.; Sousa, A. A.; Wilson, C. M.; Aronova, M. A.; Griffiths, G. L.; Leapman, R. D.; Vo, H. Q. Physiologic Upper Limit of Pore Size in the Blood-Tumor Barrier of Malignant Solid Tumors J. Transl. Med. 2009, 7, 51 10.1186/1479-5876-7-51
223. Reeves, A.; Vinogradov, S. V.; Morrissey, P.; Chernin, M.; Ahmed, M. M. Curcumin-Encapsulating Nanogels as an Effective Anticancer Formulation for Intracellular Uptake Mol. Cell. Pharmacol. 2015, 7 (3) 25-40 10.4255/mcpharmacol.15.04
224. Hu, B.; Sun, D.; Sun, C.; Sun, Y.-F.; Sun, H.-X.; Zhu, Q.-F.; Yang, X.-R.; Gao, Y.-B.; Tang, W.-G.; Fan, J.; Maitra, A.; Anders, R. A.; Xu, Y. A Polymeric Nanoparticle Formulation of Curcumin in Combination with Sorafenib Synergistically Inhibits Tumor Growth and Metastasis in an Orthotopic Model of Human Hepatocellular Carcinoma Biochem. Biophys. Res. Commun. 2015, 468 (4) 525-532 10.1016/j.bbrc.2015.10.031
225. Yallapu, M. M.; Ebeling, M. C.; Khan, S.; Sundram, V.; Chauhan, N.; Gupta, B. K.; Puumala, S. E.; Jaggi, M.; Chauhan, S. C. Novel Curcumin-Loaded Magnetic Nanoparticles for Pancreatic Cancer Treatment Mol. Cancer Ther. 2013, 12 (8) 1471-1480 10.1158/1535-7163.MCT-12-1227
226. Mignet, N.; Seguin, J.; Chabot, G. G. Bioavailability of Polyphenol Liposomes: A Challenge Ahead Pharmaceutics 2013, 5 (3) 457-471 10.3390/pharmaceutics5030457
227. Thangapazham, R. L.; Puri, A.; Tele, S.; Blumenthal, R.; Maheshwari, R. K. Evaluation of a Nanotechnology-Based Carrier for Delivery of Curcumin in Prostate Cancer Cells Int. J. Oncol. 2008, 32 (5) 1119-1123 10.3892/ijo.32.5.1119
228. Meng, E.; Hoang, T. Micro- and Nano-Fabricated Implantable Drug-Delivery Systems Ther. Delivery 2012, 3 (12) 1457-1467 10.4155/tde.12.132
229. ALZET Osmotic Pumps-Small, Infusion Pumps for Continuous Dosing of Unrestrained Laboratory Animals; ALZET: Cupertino, CA, 2017; http://www.alzet.com/ (accessed Jun 29, 2016).
230. Jain, J. P.; Modi, S.; Domb, A. J.; Kumar, N. Role of Polyanhydrides as Localized Drug Carriers J. Controlled Release 2005, 103 (3) 541-563 10.1016/j.jconrel.2004.12.021
231. Liechty, W. B.; Peppas, N. A. Expert Opinion: Responsive Polymer Nanoparticles in Cancer Therapy Eur. J. Pharm. Biopharm. 2012, 80 (2) 241-246 10.1016/j.ejpb.2011.08.004
232. Munson, P.; Shukla, A. Exosomes: Potential in Cancer Diagnosis and Therapy Med. Basel 2015, 2 (4) 310-327 10.3390/medicines2040310
233. Sun, D.; Zhuang, X.; Xiang, X.; Liu, Y.; Zhang, S.; Liu, C.; Barnes, S.; Grizzle, W.; Miller, D.; Zhang, H.-G. A Novel Nanoparticle Drug Delivery System: The Anti-Inflammatory Activity of Curcumin Is Enhanced When Encapsulated in Exosomes Mol. Ther. 2010, 18 (9) 1606-1614 10.1038/mt.2010.105
234. Taverna, S.; Giallombardo, M.; Pucci, M.; Flugy, A.; Manno, M.; Raccosta, S.; Rolfo, C.; De Leo, G.; Alessandro, R. Curcumin Inhibits in Vitro and in Vivo Chronic Myelogenous Leukemia Cells Growth: A Possible Role for Exosomal Disposal of miR-21 Oncotarget 2015, 6 (26) 21918-21933 10.18632/oncotarget.4204
235. Munagala, R.; Aqil, F.; Jeyabalan, J.; Gupta, R. C. Bovine Milk-Derived Exosomes for Drug Delivery Cancer Lett. 2016, 371 (1) 48-61 10.1016/j.canlet.2015.10.020
236. Gupta, R.; Aqil, F.; Jeyabalan, J.; Agrawal, A.; Vadhanam, M.; Munagala, R. Novel Controlled-Release Technologies to Enhance Efficacy of Polyphenols. Communication to the 7th International Conference on Polyphenols and Health. Tours, France, 2015; 2015.
237. Wang, X.; Hao, L.; Zhang, C.; Chen, J.; Zhang, P. High Efficient Anti-Cancer Drug Delivery Systems Using Tea Polyphenols Reduced and Functionalized Graphene Oxide J. Biomater. Appl. 2017, 31 (8) 1108-1122 10.1177/0885328216689364