Phenolic secoiridoids in extra virgin olive oil impede fibrogenic and oncogenic epithelial-to-mesenchymal transition: Extra virgin olive oil as a source of novel antiaging phytochemicals

Rejuvenation Research

Volumn 15, Issue 1, 2012, Pages 3-21

  Vazquez Martin, Alejandro ^a,b   Fernández Arroyo, Salvador ^c   Cufí, Sílvia ^a,b   Oliveras Ferraros, Cristina ^a,b   Lozano Sánchez, Jesús ^c   Vellón, Luciano ^d   Micol, Vicente ^e   Joven, Jorge ^f   Segura Carretero, Antonio ^c   Menendez, Javier A ^a,b  

^a CATALAN INSTITUTE OF ONCOLOGY   (Spain)

^b GIRONA BIOMEDICAL RESEARCH INSTITUTE IDIBGI   (Spain)

^c UNIVERSITY OF GRANADA   (Spain)

^d Fundacion Inbiomed   (Spain)

^e MIGUEL HERNÁNDEZ UNIVERSITY   (Spain)

^f HOSPITAL UNIVERSITARI SANT JOAN DE REUS   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

AGLYCONE; DECARBOXYMETHYL OLEUROPEIN AGLYCONE; FIBRONECTIN; OLEUROPEIN; OLEUROPEIN AGLYCONE; OLIVE OIL; PHENOL DERIVATIVE; SECOIRIDOID; SMAD4 PROTEIN; TRANSCRIPTION FACTOR SLUG; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; UVOMORULIN; VIMENTIN;

AGING; ANIMAL CELL; ARTICLE; CELL INTERACTION; CELL MIGRATION; CELL STRUCTURE; CONTROLLED STUDY; EPITHELIAL MESENCHYMAL TRANSITION; FIBROSIS; FN GENE; GENE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; IN VITRO STUDY; MEDITERRANEAN DIET; NEOPLASM; NONHUMAN; OLEACEAE; PHENOTYPE; PHYTOCHEMISTRY; PRIORITY JOURNAL; PROTEIN SYNTHESIS; SERPINE1 GENE; SIGNAL TRANSDUCTION; SNAI2 GENE; TCF4 GENE; TIME OF FLIGHT MASS SPECTROMETRY; TRANSCRIPTION REGULATION; UPREGULATION; VIM GENE;

AGING; ANIMALS; ANTICARCINOGENIC AGENTS; CELL LINE; CELL LINE, TUMOR; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DIET; DOGS; EPITHELIAL-MESENCHYMAL TRANSITION; FIBROSIS; HUMANS; IRIDOIDS; MASS SPECTROMETRY; MICROSCOPY, FLUORESCENCE; NEOPLASM METASTASIS; PHENOL; PHENOLS; PLANT OILS; REAL-TIME POLYMERASE CHAIN REACTION;

EID: 84857291584     PISSN: 15491684     EISSN: 15578577     Source Type: Journal    
DOI: 10.1089/rej.2011.1203     Document Type: Article

References (118)

1. Moustakas A, Heldin CH. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci 2007;98:1512-1520. (Pubitemid 47308444)
2. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelialmesenchymal transitions in development and disease. Cell 2009;139:871-890.
3. Kalluri R, Weinberg RA. The basics of epithelialmesenchymal transition. J Clin Invest 2009;119:1420-1428.
4. Blagosklonny MV. Validation of anti-aging drugs by treating age-related diseases. Aging (Albany NY) 2009;1:281-288.
5. Stahl PJ, Felsen D. Transforming growth factor-beta, basement membrane and epithelial-mesenchymal transdifferentiation: implications for fibrosis in kidney disease. Am J Pathol 2001;159:1187-1192. (Pubitemid 32947947)
6. Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 2002;110:341-350. (Pubitemid 34847966)
7. Zeisberg M, Yang C, Martino M, Duncan MB, Rieder F, Tanjore H, Kalluri R. Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem 2007;282:23337-23347. (Pubitemid 47311952)
8. Syn WK, Jung Y, Omenetti A, Abdelmalek M, Guy CD, Yang L, Wang J, Witek RP, Fearing CM, Pereira TA, Teaberry V, Choi SS, Conde-Vancells J, Karaca GF, Diehl AM. Hedgehog-mediated epithelial-to-mesenchymal transition and fibrogenic repair in nonalcoholic fatty liver disease. Gastroenterology 2009;137:1478-1488.e8
9. Sato M, Muragaki Y, Saika S, Roberts AB, Ooshima A. Targeted disruption of TGF-beta1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J Clin Invest 2003;112:1486-1494. (Pubitemid 38056275)
10. Yeh YC, Wei WC, Wang YK, Lin SC, Sung JM, Tang MJ. Transforming growth factor-{beta}1 induces Smad3-dependent {beta}1 integrin gene expression in epithelialto-mesenchymal transition during chronic tubulointerstitial fibrosis. Am J Pathol 2010;177:1743-1754.
11. Meindl-Beinker NM, Dooley S. Transforming growth factorbeta and hepatocyte transdifferentiation in liver fibrogenesis. J Gastroenterol Hepatol 2008;23(Suppl 1):S122-S127. (Pubitemid 351389043)
12. Ghosh AK, Bradham WS, Gleaves LA, De Taeye B, Murphy SB, Covington JW, Vaughan DE. Genetic deficiency of plasminogen activator inhibitor-1 promotes cardiac fibrosis in aged mice: involvement of constitutive transforming growth factor-beta signaling and endothelial-to-mesenchymal transition. Circulation 2010;122:1200-1209.
13. Wynn TA. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest 2007;117:524-549.
14. Bedi S, Vidyasagar A, Djamali A. Epithelial-to-mesenchymal transition and chronic allograft tubulointerstitial fibrosis. Transplant Rev (Orlando) 2008;22:1-5. (Pubitemid 350131582)
15. Djamali A, Samaniego M. Fibrogenesis in kidney transplantation: potential targets for prevention and therapy. Transplantation 2009;88:1149-1156.
16. Strutz F. Pathogenesis of tubulointerstitial fibrosis in chronic allograft dysfunction. Clin Transplant 2009; 23(Suppl 21):26-32.
17. Aguilera A, Yáñ ez-Mo M, Selgas R, Sánchez-Madrid F, López-Cabrera M. Epithelial to mesenchymal transition as a triggering factor of peritoneal membrane fibrosis and angiogenesis in peritoneal dialysis patients. Curr Opin Investig Drugs 2005;6:262-268. (Pubitemid 40424734)
18. Selgas R, Bajo A, Jiménez-Heffernan JA, Sánchez-Tomero JA, Del Peso G, Aguilera A, López-Cabrera M. Epithelialto-mesenchymal transition of the mesothelial cell-its role in the response of the peritoneum to dialysis. Nephrol Dial Transplant 2006; 21(Suppl 2):ii2-ii7. (Pubitemid 44018935)
19. Aroeira LS, Aguilera A, Sánchez-Tomero JA, Bajo MA, del Peso G, Jiménez-Heffernan JA, Selgas R, López-Cabrera M. Epithelial to mesenchymal transition and peritoneal membrane failure in peritoneal dialysis patients: Pathologic significance and potential therapeutic interventions. J Am Soc Nephrol 2007;18:2004-2013. (Pubitemid 47041064)
20. Li C, Yang CW. The pathogenesis and treatment of chronic allograft nephropathy. Nat Rev Nephrol 2009;5:513-519.
21. Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T. Opinion: migrating cancer stem cells-an integrated concept of malignant tumour progression. Nat Rev Cancer 2005;5:744-749. (Pubitemid 41486367)
22. Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelialmesenchymal transition: New insights in signaling, development, and disease. J Cell Biol 2006;172:973-981.
23. Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res 2006;66:8319-8326. (Pubitemid 44449137)
24. Moustakas A, Heldin CH. Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci 2007;98:1512-1520. (Pubitemid 47308444)
25. Guarino M, Rubino B, Ballabio G. The role of epithelialmesenchymal transition in cancer pathology. Pathology 2007;39:305-318. (Pubitemid 46897605)
26. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008;133:704-715. (Pubitemid 351636299)
27. Hollier BG, Evans K,Mani SA. The epithelial-to-mesenchymal transition and cancer stem cells: a coalition against cancer therapies. J Mammary Gland Biol Neoplasia 2009;14:29-43.
28. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010;29:4741-4751.
29. May CD, Sphyris N, Evans KW, Werden SJ, Guo W, Mani SA. Epithelial-mesenchymal transition and cancer stem cells: a dangerously dynamic duo in breast cancer progression. Breast Cancer Res 2011;13:202.
30. Kong D, Li Y, Wang Z, Sarkar FH. Cancer stem cells and epithelial-to-mesenchymal transition (EMT)-phenotypic cells: Are they cousin or twins? Cancers 2011;3:716-729.
31. Morel AP, LièvreM, ThomasC,Hinkal G, Ansieau S, Puisieux A. Generation of breast cancer stem cells through epithelialmesenchymal transition. PLoS ONE 2008;3:e2888.
32. Blick T, Hugo H, Widodo E, Waltham M, Pinto C, Mani SA, Weinberg RA, Neve RM, Lenburg ME, Thompson EW. Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44(hi/)CD24 (lo/-) stem cell phenotype in human breast cancer. J Mammary Gland Biol Neoplasia 2010;15:235-252.
33. Caja L, Bertran E, Campbell J, Fausto N, Fabregat I. The transforming growth factor-beta (TGF-b) mediates acquisition of a mesenchymal stem cell-like phenotype in human liver cells. J Cell Physiol 2011;226:1214-1223.
34. Fuxe J, Vincent T, de Herreros AG. Transcriptional crosstalk between TGFbeta and stem cell pathways in tumor cell invasion: Role of EMT promoting Smad complexes. Cell Cycle 2010;9:2363-2374.
35. Phinney DG. Twist, epithelial-to-mesenchymal transition, and stem cells. Stem Cells 2011;29:3-4.
36. Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 2009;138:645-659.
37. Wang Z, Li Y, Ahmad A, Azmi AS, Kong D, Banerjee S, Sarkar FH. Targeting miRNAs involved in cancer stem cell and EMT regulation: An emerging concept in overcoming drug resistance. Drug Resist Updat 2010;13:109-118.
38. Li Y, VandenBoom TG 2nd, Kong D, Wang Z, Ali S, Philip PA, Sarkar FH. Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-tomesenchymal transition in gemcitabine-resistant pancreatic cancer cells. Cancer Res 2009;69:6704-6712.
39. López-Novoa JM, Nieto MA. Inflammation and EMT: An alliance towards organ fibrosis and cancer progression. EMBO Mol Med 2009;1:303-314.
40. Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Antoch MP, Blagosklonny MV. Rapamycin extends maximal lifespan in cancer-prone mice. Am J Pathol 2010;176:2092-2097.
41. Blagosklonny MV. Revisiting the antagonistic pleiotropy theory of aging: TOR-driven program and quasi-program. Cell Cycle 2010;9:3151-3156.
42. Blagosklonny MV. Rapamycin and quasi-programmed aging: Four years later. Cell Cycle 2010; 9:1859-1862.
43. Aguilera A, Aroeira LS, Ramirez-Huesca M, Perez-Lozano ML, Cirugeda A, Bajo MA, Del Peso G, Valenzuela-Fernandez A, Sanchez-Tomero JA, Lopez-Cabrera M, Selgas R. Effects of rapamycin on the epithelial-tomesenchymal transition of human peritoneal mesothelial cells. Int J Artif Organs 2005;28:164-169. (Pubitemid 40485216)
44. Lamouille S, Derynck R. Emergence of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin axis in transforming growth factor-b-induced epithelial-mesenchymal transition. Cells Tissues Organs 2011; 193:8-22.
45. Menendez JA, Cufí S, Oliveras-Ferraros C, Vellon L, Joven J, Vazquez-Martin A. Gerosuppressant Metformin: Less is more. Aging (Albany NY) 2011;4:348-362.
46. Cufí S, Vazquez-Martin A, Oliveras-Ferraros C, Martin-Castillo B, Joven J, Menendez JA. Metformin against TGFbinduced epithelial-to-mesenchymal transition (EMT): From cancer stem cells to aging-associated fibrosis. Cell Cycle 2010;9:4461-4468.
47. Oliveras-Ferraros C, Cufí S, Vazquez-Martin A, Torres-Garcia VZ, Del Barco S, Martin-Castillo B, Menendez JA. Micro(mi)RNA expression profile of breast cancer epithelial cells treated with the anti-diabetic drug metformin: Induction of the tumor suppressor miRNA let-7a and suppression of the TGFb-induced oncomiR miRNA-181a. Cell Cycle 2011;10:1144-1151.
48. Vazquez-Martin A, Oliveras-Ferraros C, Cufí S, Del Barco S, Martin-Castillo B, Menendez JA. Metformin regulates breast cancer stem cell ontogeny by transcriptional regulation of the epithelial-mesenchymal transition (EMT) status. Cell Cycle 2010;9:3807-3814.
49. Vazquez-Martin A, Oliveras-Ferraros C, Del Barco S, Martin-Castillo B, Menendez JA. The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cells. Breast Cancer Res Treat 2011;126:355-364.
50. Vazquez-Martin A, Oliveras-Ferraros C, Cufí S, Martin-Castillo B, Menendez JA. Metformin and energy metabolism in breast cancer: from insulin physiology to tumourinitiating stem cells. Curr Mol Med 2010;10:674-691.
51. Jensen SR, Franzyk H, Wallander E. Chemotaxonomy of the Oleaceae: Iridoids as taxonomic markers. Phytochemistry 2002;60:213-231. (Pubitemid 34951148)
52. Bendini A, Cerretani L, Carrasco-Pancorbo A, Gómez-Caravaca AM, Segura-Carretero A, Fernández-Gutiérrez A, Lercker G. Phenolic molecules in virgin olive oils: A survey of their sensory properties, health effects, antioxidant activity and analytical methods. An overview of the last decade. Molecules 2007;12:1679-1719.
53. Lozano-Sánchez J, Segura-Carretero A, Menendez JA, Oliveras-Ferraros C, Cerretani L, Fernández-Gutiérrez A. Prediction of extra virgin olive oil varieties through their phenolic profile. Potential cytotoxic activity against human breast cancer cells. J Agric Food Chem 2010;58:9942-9955.
54. García-Villalba R, Carrasco-Pancorbo A, Oliveras-Ferraros C, Vázquez-Martín A, Menéndez JA, Segura-Carretero A, Fernández-Gutiérrez A. Characterization and quantification of phenolic compounds of extra-virgin olive oils with anticancer properties by a rapid and resolutive LC-ESITOF MS method. J Pharm Biomed Anal 2010;51:416-429.
55. Oliveras-Ferraros C, Vazquez-Martin A, Martin-Castillo B, Cufí S, Del Barco S, Lopez-Bonet E, Brunet J, Menendez JA. Dynamic emergence of the mesenchymal CD44(pos)CD24(-neg/low) phenotype in HER2-gene amplified breast cancer cells with de novo resistance to trastuzumab (Herceptin). Biochem Biophys Res Commun 2010;397:27-33.
56. Oliveras-Ferraros C, Fernández-Arroyo S, Vazquez-Martin A, Lozano-Sánchez J, Cufí S, Joven J, Micol V, Fernández- Gutiérrez A, Segura-Carretero A, Menendez JA. Crude phenolic extracts from extra virgin olive oil circumvent de novo breast cancer resistance to HER1/HER2-targeting drugs by inducing GADD45-sensed cellular stress, G2/M arrest and hyperacetylation of Histone H3. Int J Oncol 2011;38:1533-1547.
57. Singleton YL, Rossi JA. Colorimetry of total phenolics with phosphomolybdic-phosphotungtic acid reagents. Am J Enol Vitic 1965;16:144-158.
58. Fu SP, Segura-Carretero A, Arráez-Román D, Menéndez JA, De La Torre A, Fernández-Gutiérrez A. Tentative Characterization of Novel Phenolic Compounds in Extra Virgin Olive Oils by Rapid-Resolution Liquid Chromatography Coupled with Mass Spectrometry. J Agric Food Chem 2009;57:11140-11147.
59. Sobrado VR, Moreno-Bueno G, Cubillo E, Holt LJ, Nieto MA, Portillo F, Cano A. The class I bHLH factors E2-2A and E2-2B regulate EMT. J Cell Sci 2009;122:1014-1024.
60. Jayachandran A, Kö nigshoff M, Yu H, Rupniewska E, Hecker M, Klepetko W, Seeger W, Eickelberg O. SNAI transcription factors mediate epithelial-mesenchymal transition in lung fibrosis. Thorax 2009;64:1053-1061.
61. Freytag J, Wilkins-Port CE, Higgins CE, Higgins SP, Samarakoon R, Higgins PJ. PAI-1 mediates the TGF-beta1 + EGF-induced "scatter" response in transformed human keratinocytes. J Invest Dermatol 2010;130:2179-2190.
62. Senoo T, Hattori N, Tanimoto T, Furonaka M, Ishikawa N, Fujitaka K, Haruta Y, Murai H, Yokoyama A, Kohno N. Suppression of plasminogen activator inhibitor-1 by RNA interference attenuates pulmonary fibrosis. Thorax 2010;65: 334-340.
63. Chagraoui J, Lepage-Noll A, Anjo A, Uzan G, Charbord P. Fetal liver stroma consists of cells in epithelial-tomesenchymal transition. Blood 2003;101:2973-2982. (Pubitemid 36857982)
64. Saika S, Shirai K, Yamanaka O, Miyazaki K, Okada Y, Kitano A, Flanders KC, Kon S, Uede T, Kao WW, Rittling SR, Denhardt DT, Ohnishi Y. Loss of osteopontin perturbs the epithelial-mesenchymal transition in an injured mouse lens epithelium. Lab Invest 2007;87:130-138.
65. Rödder S, Scherer A, Raulf F, Berthier CC, Hertig A, Couzi L, Durrbach A, Rondeau E, Marti HP. Renal allograftswith IF/TA displaydistinctexpressionprofiles of metzincins and related genes. Am J Transplant 2009;9:517-526.
66. Das S, Becker BN, Hoffmann FM, Mertz JE. Complete reversal of epithelialto mesenchymal transitionrequiresinhibition of both ZEB expression and the Rho pathway. BMC Cell Biol 2009;10:94.
67. Belguise K, Guo S, Sonenshein GE. Activation of FOXO3a by the green tea polyphenol epigallocatechin-3-gallate induces estrogen receptor alpha expression reversing invasive phenotype of breast cancer cells. Cancer Res 2007;67:5763-5770. (Pubitemid 46985009)
68. Belguise K, Guo S, Yang S, Rogers AE, Seldin DC, Sherr DH, Sonenshein GE. Green tea polyphenols reverse cooperation between c-Rel and CK2 that induces the aryl hydrocarbon receptor, slug, and an invasive phenotype. Cancer Res 2007;67:11742-11750.
69. Xiao H, Ma X, Feng W, Fu Y, Lu Z, Xu M, Shen Q, Zhu Y, Zhang Y. Metformin attenuates cardiac fibrosis by inhibiting the TGFbeta1-Smad3 signalling pathway. Cardiovasc Res 2010;87:504-513.
70. Mishra R, Cool BL, Laderoute KR, Foretz M, Viollet B, Simonson MS. AMP-activated protein kinase inhibitstrans forming growth factor-beta-induced Smad3-dependent transcription and myofibroblast transdifferentiation. J Biol Chem 2008;283:10461-10469.
71. Collins QF, Liu HY, Pi J, Liu Z, Quon MJ, Cao W Epigallocatechin-3- gallate (EGCG), a green tea polyphenol, suppresses hepatic gluconeogenesis through 5¢-AMP-activated protein kinase. J Biol Chem 2007;282:30143-30149. (Pubitemid 350035266)
72. Murase T, Misawa K, Haramizu S, Hase T. Catechininduced activation of the LKB1/AMP-activated protein kinase pathway. Biochem Pharmacol 2009;78:78-84.
73. Huang CH, Tsai SJ, Wang YJ, Pan MH, Kao JY, Way TD. EGCG inhibits protein synthesis, lipogenesis, and cell cycle progression through activation of AMPK in p53 positive and negative human hepatoma cells. Mol Nutr Food Res 2009;53:1156-1165.
74. Nerstedt A, Johansson A, Andersson CX, Cansby E, Smith U, Mahlapuu M. AMP-activated protein kinase inhibits IL-6-stimulated inflammatory response in human liver cells by suppressing phosphorylation of signal transducer and activator of transcription 3 (STAT3). Diabetologia 2010;53: 2406-2416.
75. Lo HW, Hsu SC, Xia W, Cao X, Shih JY, Wei Y, Abbruzzese JL, Hortobagyi GN, Hung MC. Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer Res 2007;67:9066-9076. (Pubitemid 47535891)
76. Sullivan NJ, Sasser AK, Axel AE, Vesuna F, Raman V, Ramirez N, Oberyszyn TM, Hall BM. Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. Oncogene 2009;28:2940-2947.
77. Shankar S, Nall D, Tang S-N, Meeker D, Passarini J, Sharma J, Srivastava RK. Resveratrol inhibits pancreatic cancer stem cell characteristics in human and KrasG12D transgenic mice by inhibiting pluripotency maintaining factors and epithelial-mesenchymal transition. PLoS One 2011;6:e16530.
78. Tryndyak VP, Beland FA, Pogribny IP. E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. Int J Cancer 2010;126:2575-2583.
79. Li J, Qu X, Ricardo SD, Bertram JF, Nikolic-Paterson DJ. Resveratrol inhibits renal fibrosis in the obstructed kidney: Potential role in deacetylation of Smad3. Am J Pathol 2010;177:1065-1071.
80. Li C, Cai F, Yang Y, Zhao X, Wang C, Li J, Jia Y, Tang J, Liu Q. Tetrahydroxystilbene glucoside ameliorates diabetic nephropathy in rats: involvement of SIRT1 and TGF-b1 pathway. Eur J Pharmacol 2010;649:382-389.
81. Tang SN, Singh C, Nall D, Meeker D, Shankar S, Srivastava RK.The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelialmesenchymal transition. J Mol Signal 2010;5:14.
82. Srivastava RK, Tang SN, Zhu W, Meeker D, Shankar S. Sulforaphane synergizes with quercetin to inhibit selfrenewal capacity of pancreatic cancer stem cells. Front Biosci (Elite Ed) 2011;3:515-528.
83. Turner N, Li JY, Gosby A, To SW, Cheng Z, Miyoshi H, Taketo MM, Cooney GJ, Kraegen EW, James DE, Hu LH, Li J, Ye JM. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: A mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes 2008;57:1414-1418.
84. Gledhill JR, Montgomery MG, Leslie AG, Walker JE. Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. Proc Natl Acad Sci USA 2007;104: 13632-13637. (Pubitemid 350003372)
85. Hwang JT, Kwon DY, Yoon SH. AMP-activated protein kinase: A potential target for the diseases prevention by natural occurring polyphenols. New Biotechnol 2009;26:17-22.
86. Lee KW, Lee HJ. The roles of polyphenols in cancer chemoprevention. Biofactors 2006;26:105-121.
87. Rahman I, Biswas SK, Kirkham PA. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol 2006;72:1439-1452. (Pubitemid 44666744)
88. Page MM, Robb EL, Salway KD, Stuart JA. Mitochondrial redox metabolism: Aging, longevity and dietary effects. Mech Ageing Dev 2010;131:242-252.
89. Katsiki M, Chondrogianni N, Chinou I, Rivett AJ, Gonos ES. The olive constituent oleuropein exhibits proteasome stimulatory properties in vitro and confers life span extension of human embryonic fibroblasts. Rejuvenation Res 2007;10:157-172. (Pubitemid 46944984)
90. Paiva-Martins F, Fernandes J, Rocha S, Nascimento H, Vitorino R, Amado F, Borges F, Belo L, Santos-Silva A. Effects of olive oil polyphenols on erythrocyte oxidative damage. Mol Nutr Food Res 2009;53:609-616.
91. Stefanatos R, Sanz A. Mitochondrial complex I: A central regulator of the aging process. Cell Cycle 2011;10.
92. Fulco M, Cen Y, Zhao P, Hoffman EP, McBurney MW, Sauve AA, Sartorelli V. Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPKmediated regulation of Nampt. Dev Cell 2008;14:661-673. (Pubitemid 351622608)
93. Guarente L. Connecting the dots: Linking sirtuins and AMPK in metabolism and aging. Dev Cell 2011; 20:e1.
94. Wang Y, Liang Y, Vanhoutte PM. SIRT1 and AMPK in regulating mammalian senescence: A critical review and a working model. FEBS Lett 2011;585:986-994.
95. Scheepens A, Tan K, Paxton JW. Improving the oral bioavailability of beneficial polyphenols through designed synergies. Genes Nutr 2010;5:75-87.
96. Vauzour D, Rodriguez-Mateos A, Corona G, Oruna-Concha MJ, Spencer JPE. Polyphenols and human health: Prevention of disease and mechanisms of action. Nutrients 2010;2:1106-1131.
97. Visioli F, de la Lastra CA, Andres-Lacueva X, 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;51:524-546.
98. Vissers MN, Zock PL, Roodenburg AJC, Leenen R, Katan, MB. Olive oil phenols are absorbed in humans. J Nutr 2002;132:409-417. (Pubitemid 34208742)
99. Zhang L, Zuo Z, Lin G. Intestinal and hepatic glucuronidation of flavonoids. Mol Pharm 2007;4:833-845.
100. Lambert JD, Sang SM, Yang CS. Biotransformation of green tea polyphenols and the biological activities of those metabolites, Mol Pharmaceutics 2007;4:819-825.
101. Landis-Piwowar KR, Dou QP. Polyphenols: Biological activities, molecular targets, and the effect of methylation. Curr Mol Pharmacol 2008;1:233-243.
102. Chang HC, Churchwell MI, Delclos KB, Newbold RR, Doerge DR. Mass spectrometric determination of Genistein tissue distribution in diet exposed Sprague-Dawley rats. J Nutr 2000;130:1963-1970. (Pubitemid 30497528)
103. Datla KP, Christidou M, Widmer WW, Rooprai HK, Dexter DT. Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease. Neuroreport 2001;12:3871-3875. (Pubitemid 33105188)
104. Schramm D, Collins H, German B. Flavonoid transport by mammalian endothelial cells. J Nutr Biochem 1999;10: 193-197. (Pubitemid 29146056)
105. Suganuma M, Okabe S, Oniyama M, Tada Y, Ito H, Fujiki H. Wide distribution of [3H](-)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis 1998;19:1771-1776. (Pubitemid 28476352)
106. Gao S, Hu M. Bioavailability challenges associated with development of anti-cancer phenolics. Mini Rev Med Chem 2010;10:550-567.
107. Selma MV, Espin JC, Tomas-Barberan FA. Interaction between phenolics and gut microbiota: role in human health. J Agric Food Chem 2009;57:6485-6501.
108. Singh J, Dubey RK, Atal CK. Piperine-mediated inhibition of glucuronidation activity in isolated epithelial cells of the guinea-pig small intestine: evidence that piperine lowers the endogeneous UDP-glucuronic acid content. J Pharmacol Exp Ther 1986;236:488-493. (Pubitemid 16184247)
109. Reen RK, Jamwal DS, Taneja SC, Koul JL, Dubey RK, Wiebel FJ, Singh J. Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver and small intestine of rat and guinea pig in vitro by piperine. Biochem Pharmacol 1993;46:229-238. (Pubitemid 23218606)
110. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998;64:353-356. (Pubitemid 28234275)
111. Lambert JD, Hong J, Kim DH, Mishin VM, Yang CS. Piperine enhances the bioavailability of the tea polyphenol (-)-epigallocatechin-3-gallate in mice. J Nutr 2004;134:1948-1952. (Pubitemid 39031322)
112. Johnson JJ, Nihal M, Siddiqui IA, Scarlett CO, Bailey HH, Mukhtar H, Ahmad N. Enhancing the bioavailability of resveratrol by combining it with piperine. Mol Nutr Food Res 2011;55:1169-1176.
113. Nair HB, Sung B, Yadav VR, Kannappan R, Chaturvedi MM, Aggarwal BB. Delivery of antiinflammatory nutraceuticals by nanoparticles for the prevention and treatment of cancer. Biochem Pharmacol 2010;80:1833-1843.
114. Goulas V, Exarchou V, Troganis AN, Psomiadou E, Fotsis T, Briasoulis E, Gerothanassis IP. Phytochemicals in oliveleaf extracts and their antiproliferative activity against cancer and endothelial cells. Mol Nutr Food Res 2009;53: 600-608.
115. Menendez JA, Vazquez-Martin A, Colomer R, Brunet J, Carrasco-Pancorbo A, Garcia-Villalba R, Fernandez-Gutierrez A, Segura-Carretero A. Olive oil's bitter principle reverses acquired autoresistance to trastuzumab (Herceptin) in HER2-overexpressing breast cancer cells. BMC Cancer 2007;7:80.
116. Menendez JA, Vazquez-Martin A, Oliveras-Ferraros C, Garcia-Villalba R, Carrasco-Pancorbo A, Fernandez-Gutierrez A, Segura-Carretero A. Analyzing effects of extra-virgin olive oil polyphenols on breast cancer-associated fatty acid synthase protein expression using reverse-phase protein microarrays. Int J Mol Med 2008;22:433-439.
117. Menendez JA, Vazquez-Martin A, Oliveras-Ferraros C, Garcia-Villalba R, Carrasco-Pancorbo A, Fernandez-Gutierrez A, Segura-Carretero A. Extra-virgin olive oil polyphenols inhibit HER2 (erbB-2)-induced malignant transformation in human breast epithelial cells: relationship between the chemical structures of extra-virgin olive oil secoiridoids and lignans and their inhibitory activities on the tyrosine kinase activity of HER2. Int J Oncol 2009;34:43-51.
118. Menendez JA, Vazquez-Martin A, Garcia-Villalba R, Carrasco-Pancorbo A, Oliveras-Ferraros C, Fernandez-Gutierrez A, Segura-Carretero A. Anti-HER2 (erbB-2) oncogene effects of phenolic compounds directly isolated from commercial Extra-Virgin Olive Oil (EVOO). BMC Cancer 2008;8:377.