Impaired expressionFabio and function of signaling pathway enzymes by anthocyanins: Role on cancer prevention and progression

Current Enzyme Inhibition

Volumn 5, Issue 4, 2009, Pages 184-197

  Bei, Roberto ^a   Masuelli, Laura ^b   Turriziani, Mario ^a   Volti, Giovanni Li ^c   Malaguarnera, Michele ^c   Galvano, Fabio ^c  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

^c UNIVERSITY OF CATANIA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTHOCYANIN; CYANIDIN; CYANIDIN 3 GALACTOSIDE; CYANIDIN 3 GLUCOSIDE; CYANIDIN 3 O GLUCOSIDE; CYANIDIN 3 RUTIN; CYANIDIN 3 RUTINOSIDE; CYANIDIN 3,5 DIGLUCOSIDE; CYANIDIN CHLORIDE; CYTOCHROME P450 3A4; DELPHINIDIN; DELPHINIDIN 3 GLUCOSIDE; DELPHINIDIN 3 O GLUCOSIDE; DELPHININ; DNA TOPOISOMERASE; FLAVONOID; KAEMPFERIDINIDIN; MALVIDIN 3 GALACTOSIDE; MALVIDIN 3 GLUCOSIDE; MALVIDIN 3,5 DIGLUCOSIDE; MALVIDIN CHLORIDE; PELAGORDININ; PELARGONIDIN 3,5 DIGLUCOSIDE; PEONIDIN; PEONIDIN 3 GLUCOSIDE; PETUNIDIN CHLORIDE; PROCYANIDIN B1; PROCYANIDIN B2; PRODELPHINIDIN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; CANCER GROWTH; CANCER INHIBITION; CANCER PREVENTION; CARCINOGENESIS; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; NONHUMAN; PATENT; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION;

EID: 73449131900     PISSN: 15734080     EISSN: None     Source Type: Journal    
DOI: 10.2174/157340809789630253     Document Type: Review

References (100)

1. Bertram, J.S. The molecular biology of cancer. Mol. Aspects Med., 2000, 21, 167-223.
2. Franco, R.; Schoneveld, O.; Georgakilas, A.G.; Panayiotidis, M.I. Oxidative stress, DNA methylation and carcinogenesis. Cancer Lett., 2008, 266, 6-11.
3. Shimada, T. Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons. Drug. Metab. Pharmacokinet., 2006, 21, 257-276.
4. McKay, M.M.; Morrison, D.K. Integrating signals from RTKs to ERK/MAPK. Oncogene, 2007, 26, 3113-3121.
5. Roberts, P.J.; Der, C.J. Targeting the Raf-MEK-ERK mitogenactivated protein kinase cascade for the treatment of cancer. Oncogene, 2007, 26, 3291-3310.
6. Miloso, M.; Tredici, G. MAPKs and their inhibitors in neuronal differentiation. Curr. Enzyme Inhib., 2007, 3, 298-308.
7. Klaunig, J.E.; Kamendulis, L.M. The role of oxidative stress in carcinogenesis. Annu. Rev. Pharmacol. Toxicol., 2004, 44, 239-267.
8. Sarkar. F.H.; Li, Y.; Wang, Z.; Kong, D. NF-kappaB signaling pathway and its therapeutic implications in human diseases. Int. Rev. Immunol., 2008, 27, 293-319.
9. Krakauer, T. Nuclear factor-kappaB: fine-tuning a central integrator of diverse biologic stimuli. Int. Rev. Immunol., 2008, 27, 286-292.
10. Chen, F.; Beezhold, K.; Castranova, V. Tumor promoting or tumor suppressing of NF-kappa B, a matter of cell context dependency. Int. Rev. Immunol., 2008, 27, 183-204.
11. Biswas, D.K.; Iglehart, J.D. Linkage between EGFR family receptors and nuclear factor kappaB (NF-kappaB) signaling in breast cancer. J. Cell. Physiol., 2006, 209, 645-652.
12. Baker, S.J.; Rane, S.G.; Reddy, E.P. Hematopoietic cytokine receptor signaling. Oncogene. 2007, 26, 6724-6737.
13. Fritz, J.; Kern, M.; Pahlke, G.; Vatter, S.; Marko, D. Biological activities of malvidin, a red wine anthocyanidin. Mol. Nutr. Food Res., 2006, 50, 390-395.
14. Nyberg, P.; Salo, T.; Kalluri, R. Tumor microenvironment and angiogenesis. Front. Biosci., 2008, 13, 6537-6553.
15. Kundu, J.K.; Surh, Y.J. Inflammation: gearing the journey to cancer. Mutat. Res., 2008, 659, 15-30.
16. Sica, A.; Allavena, P.; Mantovani, A. Cancer related inflammation: the macrophage connection. Cancer Lett., 2008, 267, 204-215.
17. Pan, M.H.; Ho, C.T. Chemopreventive effects of natural dietary compounds on cancer development. Chem. Soc. Rev., 2008, 37, 2558-2574.
18. Lee, K.W.; Lee, H.J. The roles of polyphenols in cancer chemoprevention. Biofactors, 2006, 26, 105-121.
19. Ramos, S. Cancer chemoprevention and chemotherapy: dietary polyphenols and signalling pathways. Mol. Nutr. Food. Res., 2008, 52, 507-526.
20. Wang, L.S.; Stoner. G.D. Anthocyanins and their role in cancer prevention. Cancer Lett., 2008, 269, 281-290.
21. Galvano, F.; La Fauci, L.; Vitaglione, P.; Fogliano, V.; Vanella, L.; Felgines, C. Bioavailability, antioxidant and biological properties of the natural free-radical scavengers cyanidin and related glycosides. Ann. Ist. Super. Sanità, 2007, 43, 382-393.
22. Moon, Y.J.; Wang, X.; Morris, M.E. Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol. In Vitro, 2006, 20, 187-210.
23. Dreiseitel, A.; Schreier, P.; Oehme, A.; Locher, S.; Hajak, G.; Sand, P.G. Anthocyanins and their metabolites are weak inhibitors of cytochrome P450 3A4. Mol. Nutr. Food Res., 2008, 52, 1428-1433.
24. Gasiorowski, K.; Szyba, K.; Brokos, B.; Ko??aczy??ska, B.; Jankowiak-W??odarczyk, M.; Oszmia??ski, J. Antimutagenic activity of anthocyanins isolated from Aronia melanocarpa fruits. Cancer Lett., 1997, 119, 37-46.
25. Renis, M.; Calandra, L.; Scifo, C.; Tomasello, B.; Cardile, V.; Vanella, L.; Bei, R.; La Fauci, L.; Galvano, F. Response of cell cycle/ stress-related protein expression and DNA damage upon treatment of CaCo2 cells with anthocyanins. Br. J. Nutr., 2008, 100, 27-35.
26. Champoux, J.J. DNA topoisomerases: Structure, function, and mechanism. Annu. Rev. Biochem., 2001, 70, 369-413.
27. Felix, C.A.; Lange,B.J.; Hosler, M.R.; Fertala, J.; Bjornsti, M.A. Chromosome band 11q23 translocation breakpoints are DNA topoisomerase II cleavage sites. Cancer Res., 1995, 55, 4287-4292.
28. Ferguson, L.R.; Baguley, B.C. Topoisomerase II enzymes and mutagenicity. Environ. Mol. Mutagen., 1994, 24, 245-261
29. Spector, L.G.; Xie, Y.; Robison, L.L.; Heerema, N.A.; Hilden, J.M.; Lange, B.; Felix, C.A.; Davies, S.M.; Slavin, J.; Potter, J.D.; Blair, C.K.; Reaman, G.H.; Ross, J.A. Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children's oncology group. Cancer Epidemiol. Biomarkers Prev., 2005, 14, 651-655.
30. Pungitore, C.R. Natural products as inhibitors of DNA related enzymes. Curr. Enzyme Inhib., 2008, 4, 194-215.
31. Fridrich, D.; Kern, M.; Fritz, J.; Pahlke, G.; Köhler, N.; Winterhalter, P.; Marko, D. The epidermal growth factor receptor and human topoisomerases represent potential cellular targets of oligomeric procyanidins. Mol. Nutr. Food Res., 2007, 51, 192-200.
32. Habermeyer, M.; Fritz, J.; Barthelmes, H.U.; Christensen, M.O.; Larsen, M.K.; Boege, F.; Marko, D. Anthocyanidins modulate the activity of human DNA topoisomerases I and II and affect cellular DNA integrity. Chem. Res. Toxicol., 2005, 18, 1395-1404.
33. Esselen, M.; Fritz, J.; Hutter, M.; Marko, D. Delphinidin modulates the DNA-damaging properties of topoisomerase II poisons. Chem. Res. Toxicol., 2009 Jan 30. [Epub ahead of print]
34. Fimognari, C.; Lenzi, M.; Hrelia, P. Chemoprevention of cancer by isothiocyanates and anthocyanins: mechanisms of action and structure-activity relationship. Curr. Med. Chem., 2008, 15, 440-447.
35. Hou, D.X.; Fujii, M.; Terahara, N.; Yoshimoto, M. Molecular mechanisms behind the chemopreventive effects of anthocyanidins. J. Biomed. Biotechnol., 2004, 321-325.
36. Cooke, D.; Steward, W.P.; Gescher, A.J.; Marczylo, T. Anthocyans from fruits and vegetables--does bright colour signal cancer chemopreventive activity? Eur. J. Cancer, 2005, 41, 1931-1940.
37. Nagase, H.; Sasaki, K.; Kito, H.; Haga, A.; Sato, T. Inhibitory effect of delphinidin from Solanum melongena on human fibrosarcoma HT-1080 invasiveness in vitro. Planta Med., 1998, 64, 216-219.
38. Sipeki, S.; Bander, E.; Ways, D.K.; Faragó, A. Activation of Erk1/Erk2 and transiently increased p53 levels together may account for p21 expression associated with phorbol ester-induced transient growth inhibition in HepG2 cells. Cell Signal., 2002, 14, 115-121.
39. 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 factorkappaB signaling. Cancer Res., 2008, 68, 8564-8572.
40. Hafeez, B.B.; Asim, M.; Siddiqui, I.A.; Adhami, V.M.; Murtaza, I.; Mukhtar, H. Delphinidin, a dietary anthocyanidin in pigmented fruits and vegetables: a new weapon to blunt prostate cancer growth. Cell Cycle, 2008, 7, 3320-3326.
41. Yun, J.M.; Afaq, F.; Khan, N.; Mukhtar, H. Delphinidin, an anthocyanidin in pigmented fruits and vegetables, induces apoptosis and cell cycle arrest in human colon cancer HCT116 cells. Mol. Carcinog., 2009, 48, 260-270.
42. Ding, M.; Feng, R.; Wang, S.Y.; Bowman, L.; Lu, Y.; Qian, Y.; Castranova, V.; Jiang, B.H.; Shi, X. Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity. J. Biol. Chem., 2006, 281, 17359-17368.
43. Marko, D.; Puppel, N.; Tjaden, Z.; Jakobs, S.; Pahlke, G. The substitution pattern of anthocyanidins affects different cellular signaling cascades regulating cell proliferation. Mol. Nutr. Food Res., 2004, 48, 318-325.
44. Kuo, P.L.; Hsu, Y.L.; Lin, T.C.; Lin, C.C. Prodelphinidin B-2 3,3'-di-O-gallate from Myrica rubra inhibits proliferation of A549 carcinoma cells via blocking cell cycle progression and inducing apoptosis. Eur. J. Pharmacol., 2004, 501, 41-48.
45. Wu. Q.K.; Koponen, J.M.; Mykkänen, H.M.; Törrönen, A.R. Berry phenolic extracts modulate the expression of p21(WAF1) and Bax but not Bcl-2 in HT-29 colon cancer cells. J. Agric. Food Chem., 2007, 55, 1156-1163.
46. Malik, M.; Zhao, C.; Schoene, N.; Guisti, M.M.; Moyer, M.P.; Magnuson, B.A. Anthocyanin-rich extract from Aronia meloncarpa E induces a cell cycle block in colon cancer but not normal colonic cells. Nutr. Cancer, 2003, 46, 186-196.
47. Huang, H.P.; Shih, Y.W.; Chang, Y.C.; Hung, C.N.; Wang, C.J. Chemoinhibitory effect of mulberry anthocyanins on melanoma metastasis involved in the Ras/PI3K pathway. J. Agric. Food Chem., 2008, 56, 9286-9293.
48. Chen, P.N.; Chu, S.C.; Chiou, H.L.; Kuo, W.H.; Chiang, C.L.; Hsieh, Y.S. Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line. Cancer Lett., 2006, 235, 248-259
49. Hou, D.X. Potential mechanisms of cancer chemoprevention by anthocyanins. Curr. Mol. Med., 2003, 3, 149-159.
50. Peruzzi, B.; Bottaro, D.P. Targeting the c-Met signaling pathway in cancer. Clin. Cancer Res., 2006, 12, 3657-3660.
51. Rogers, S.J.; Box, C.; Nutting, C.M.; Kevin, J.; Harrington, K.J.; Eccles, S.A. MET and RON receptor tyrosine kinases: novel therapeutic targets in squamous cell carcinoma of the head and neck. Curr. Enzyme Inhib., 2007, 3, 1-12.
52. Stellrecht, C.M.; Gandhi, V. MET receptor tyrosine kinase as a therapeutic anticancer target. Cancer Lett., 2008, Dec 17. [Epub ahead of print]
53. Syed, D.N.; Afaq, F.; Sarfaraz, S.; Khan, N.; Kedlaya, R.; Setaluri, V.; Mukhtar, H. Delphinidin inhibits cell proliferation and invasion via modulation of Met receptor phosphorylation. Toxicol. Appl. Pharmacol., 2008, 231, 52-60.
54. Hynes, N.E.; Macdonald, G. ErbB receptors and signaling pathways in cancer. Curr. Opin. Cell Biol., 2009, Feb 7. [Epub ahead of print]
55. Afaq, F.; Zaman, N.; Khan, N.; Syed, D.N.; Sarfaraz. S.; Zaid, M.A.; Mukhtar, H. Inhibition of epidermal growth factor receptor signaling pathway by delphinidin, an anthocyanidin in pigmented fruits and vegetables. Int. J. Cancer, 2008, 123, 1508-1515.
56. Meiers, S.; Kemény, M.; Weyand, U.; Gastpar, R.; von Angerer, E.; Marko, D. The anthocyanidins cyanidin and delphinidin are potent inhibitors of the epidermal growth-factor receptor. J. Agric. Food Chem., 2001, 49, 958-962.
57. Fridrich, D.; Teller, N.; Esselen, M.; Pahlke, G.; Marko, D. Comparison of delphinidin, quercetin and (-)-epigallocatechin-3-gallate as inhibitors of the EGFR and the ErbB2 receptor phosphorylation. Mol. Nutr. Food Res., 2008, 52, 815-822.
58. Gerner, E.W.; Meyskens, F.L. Jr. Polyamines and cancer: old molecules, new understanding. Nat. Rev. Cancer., 2004, 4, 781-792.
59. Afaq, F.; Saleem, M.; Krueger, C.G.; Reed, J.D.; Mukhtar, H. Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract modulates MAPK and NF-kappaB pathways and inhibits skin tumorigenesis in CD-1 mice. Int. J. Cancer, 2005, 113, 423-433.
60. Thole, J.M.; Kraft, T.F.; Sueiro, L.A.; Kang, Y.H.; Gills, J.J.; Cuendet, M.; Pezzuto, J.M.; Seigler, D.S.; Lila, M.A. A comparative evaluation of the anticancer properties of European and American elderberry fruits. J. Med. Food, 2006, 9, 498-504.
61. Bomser, J.; Madhavi, D.L.; Singletary, K.; Smith, M.A. In vitro anticancer activity of fruit extracts from Vaccinium species. Planta Med., 1996 62, 212-216.
62. Lugnier, C. Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. Pharmacol. Ther., 2006, 109, 366-368.
63. Marko, D.; Romanakis, K.; Zankl, H.; Fürstenberger, G.; Steinbauer, B.; Eisenbrand, G. Induction of apoptosis by an inhibitor of cAMP-specific PDE in malignant murine carcinoma cells overexpressing PDE activity in comparison to their nonmalignant counterparts. Cell Biochem. Biophys., 1998, 28, 75-101.
64. Rajkumar, S.V.; Richardson, P.G.; Hideshima, T.; Anderson, K.C. Proteasome inhibition as a novel therapeutic target in human cancer. J. Clin. Oncol., 2005, 23, 630-639.
65. Palumbo, C.; Bei, R.; Procopio, A.; Modesti, A. Molecular targets and targeted therapies for malignant mesothelioma. Curr. Med. Chem., 2008, 15, 855-867.
66. Dreiseitel, A.; Schreier, P.; Oehme, A.; Locher, S.; Rogler, G.; Piberger, H.; Hajak, G.; Sand, P.G. Inhibition of proteasome activity by anthocyanins and anthocyanidins. Biochem. Biophys. Res. Commun., 2008, 372, 57-61.
67. Lamy, S.; Blanchette, M.; Michaud-Levesque, J.; Lafleur, R.; Durocher, Y.; Moghrabi, A.; Barrette, S.; Gingras, D.; Béliveau, R. Delphinidin, a dietary anthocyanidin, inhibits vascular endothelial growth factor receptor-2 phosphorylation. Carcinogenesis, 2006, 27, 989-996. [68] Lamy, S.; Beaulieu, E.; Labbé, D.; Bédard, V.; Moghrabi, A.; Barrette, S.; Gingras, D.; Béliveau, R. Delphinidin, a dietary anthocyanidin, inhibits platelet-derived growth factor ligand/receptor (PDGF/PDGFR) signaling. Carcinogenesis, 2008, 29, 1033-1041.
68. Martin, S.; Giannone, G.; Andriantsitohaina, R.; Martinez, M.C. Delphinidin, an active compound of red wine, inhibits endothelial cell apoptosis via nitric oxide pathway and regulation of calcium homeostasis. Br. J. Pharmacol., 2003, 139, 1095-1102
69. Matsubara, K.; Kaneyuki, T.; Miyake, T.; Mori, M. Antiangiogenic activity of nasunin, an antioxidant anthocyanin, in eggplant peels. J. Agric. Food Chem., 2005, 53, 6272-6275.
70. Favot, L.; Martin, S., Keravis, T.; Andriantsitohaina, R.; Lugnier, C. Involvement of cyclin-dependent pathway in the inhibitory effect of delphinidin on angiogenesis. Cardiovasc. Res., 2003, 59, 479-487.
71. Spicer, J.; Chowdhury, S.; Harper, P. Targeting novel and established therapies for non-small cell lung cancer. Cancer Lett., 2007, 250, 9-16.
72. Board, R.; Jayson. G.C. Platelet-derived growth factor receptor (PDGFR): a target for anticancer therapeutics. Drug. Resist. Updat., 2005, 8, 75-83.
73. Matsumoto, T.; Mugishima, H.J. Signal transduction via vascular endothelial growth factor (VEGF) receptors and their roles in atherogenesis. Atheroscler. Thromb., 2006, 13, 130-135.
74. Oak, M.H.; Bedoui, J.E.; Madeira, S.V.; Chalupsky, K.; Oak, M.H.; Bedoui, J.E.; Madeira, S.V.; Chalupsky, K.; Schini-Kerth, V.B. Delphinidin and cyanidin inhibit PDGF(AB)-induced VEGF release in vascular smooth muscle cells by preventing activation of p38 MAPK and JNK. Br. J. Pharmacol., 2006, 149, 283-290.
75. Martin, S; Favot, L; Matz, R; Lugnier, C; Andriantsitohaina, R. Delphinidin inhibits endothelial cell proliferation and cell cycle progression through a transient activation of ERK-1/-2. Biochem. Pharmacol., 2003, 65, 669-675.
76. Chen, P.N.; Kuo, W.H.; Chiang, C.L.; Chiou, H.L.; Hsieh, Y.S.; Chu, S.C. Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and u-PA expression. Chem. Biol. Interact., 2006, 163, 218-229.
77. Bei, R.; Masuelli, L.; Palumbo, C; Tresoldi, I.; Scardino, A.; Modesti, A. Long-lasting tissue inflammatory processes trigger autoimmune responses to extracellular matrix molecules. Int. Rev. Immunol., 2008, 27, 137-175.
78. Lamy, S.; Lafleur, R.; Bédard, V.; Moghrabi, A.; Barrette, S.; Gingras, D.; Béliveau, R. Anthocyanidins inhibit migration of glioblastoma cells: structure-activity relationship and involvement of the plasminolytic system. J. Cell. Biochem., 2007, 100, 100-111.
79. Mantovani, A.; Allavena. P.; Sica, A.; Balkwill, F. Cancer-related inflammation. Nature, 2008, 454, 436-444.
80. Bei, R.; Masuelli, L.; Palumbo, C.; Modesti, M.; Modesti, A. A common repertoire of autoantibodies is shared by cancer and autoimmune disease patients: Inflammation in their induction and impact on tumor growth. Cancer Lett., 2008 Dec 15. [Epub ahead of print]
81. Karin, M.; Cao, Y.; Greten, F.R.; Li, Z.W. NF-kappaB in cancer: from innocent bystander to major culprit. Nat. Rev. Cancer, 2002, 2, 301-310.
82. Naugler, W.E.; Karin M. NF-kappaB and cancer-identifying targets and mechanisms. Curr. Opin. Genet. Dev., 2008, 18, 19-26.
83. Hecht, S.S.; Huang, C.; Stoner, G.D.; Li, J.; Kenney, P.M.; Sturla, S.J.; Carmella, S.G. Identification of cyanidin glycosides as constituents of freeze-dried black raspberries which inhibit antibenzo[a]pyrene-7,8-diol-9,10- epoxide induced NFkappaB and AP-1 activity. Carcinogenesis, 2006, 27, 1617-1626.
84. Kim, H.J.; Tsoy, I.; Park, J.M.; Chung, J.I.; Shin, S.C.; Chang, K.C. Anthocyanins from soybean seed coat inhibit the expression of TNF-alpha-induced genes associated with ischemia/reperfusion in endothelial cell by NF-kappaB-dependent pathway and reduce rat myocardial damages incurred by ischemia and reperfusion in vivo. FEBS Lett., 2006, 580, 1391-1397.
85. 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. (Phila Pa), 2009, 2, 84-93.
86. Wang, D.; Dubois, R.N. Prostaglandins and cancer. Gut, 2006, 55, 115-122.
87. Poligone, B.; Baldwin, A.S. Positive and negative regulation of NF-kappaB by COX-2: roles of different prostaglandins. J. Biol. Chem., 2001, 276, 38658-38664.
88. Pradono, P.; Tazawa, R.; Maemondo, M.; Tanaka, M.; Usui, K.; Saijo, Y.; Hagiwara, K.; Nukiwa, T. Gene transfer of thromboxane A(2) synthase and prostaglandin I(2) synthase antithetically altered tumor angiogenesis and tumor growth. Cancer Res., 2002, 62, 63-66.
89. Tsoyi, K.; Park, H.B.; Kim, Y.M.; Chung, J.I.; Shin, S.C.; Lee, W.S.; Seo, H.G.; Lee, J.H.; Chang, K,C.; Kim, H.J.J. Anthocyanins from black soybean seed coats inhibit UVB-induced inflammatory cylooxygenase-2 gene expression and PGE2 production through regulation of the nuclear factor-kappaB and phosphatidylinositol 3-kinase/Akt pathway. J. Agric. Food Chem., 2008, 56, 8969-8974.
90. Seeram, N.P.; Momin, R.A.; Nair, M.G.; Bourquin, L.D. Cyclooxygenase inhibitory and antioxidant cyanidin glycosides in cherries and berries. Phytomedicine, 2001, 8, 362-369.
91. Kwon, J.Y.; Lee, K.W.; Hur, H.J.; Lee, H.J. Peonidin inhibits phorbol-ester-induced COX-2 expression and transformation in JB6 P+ cells by blocking phosphorylation of ERK-1 and -2. Ann. N.Y. Acad. Sci., 2007, 1095, 513-520.
92. Hou, D.X.; Luo, D.; Tanigawa, S.; Hashimoto, F.; Uto, T.; Masuzaki, S.; Fujii, M.; Sakata, Y. Prodelphinidin B-4 3'-O-gallate, a tea polyphenol, is involved in the inhibition of COX-2 and iNOS via the downregulation of TAK1-NF-kappaB pathway. Biochem. Pharmacol., 2007, 74, 742-751.
93. Knaup, B.; Oehme, A.; Valotis, A.; Schreier, P. Anthocyanins as lipoxygenase inhibitors. Mol. Nutr. Food Res., 2008, Dec 15. [Epub ahead of print]
94. Wymann, M.P.; Schneiter, R. Lipid signalling in disease. Nat. Rev. Mol. Cell. Biol., 2008, 9, 162-176.
95. McGhie, T.K.; Walton, M.C. The bioavailability and absorption of anthocyanins: towards a better understanding. Mol. Nutr. Food Res., 2007, 51, 702-713.
96. Seeram, N.P.; Bourquin, L.D. ; Nair, G.M. Degradation products of cyanidin glycosides from tart cherries and their bioactivities. J. Agric. Food. Chem., 2001, 49, 4924-4929.
97. Vitaglione, P.; Donnarumma, G.; Napolitano, A.; Galvano, F.; Gallo, A.; Scalfi, L.; Fogliano, V. Protocatechuic acid is the major human metabolite of cyanidin-glucoside. J. Nutr., 2007, 137, 2043-2048.
98. Riso, P.; Visioli, F.; Gardana, C.; Grande, S.; Brusamolino, A.; Galvano, F.; Galvano, G.; Porrini, M. Effects of blood orange juice intake on antioxidant bioavailability and on different markers related to oxidative stress. J. Agric. Food. Chem., 2005, 53, 941-947.
99. Galvano, F.; Vitaglione, P.; Di Giacomo, C.; Gazzolo, D.; Li Volti, G.; Vanella, L.; La Fauci, L.; Fogliano, V. Protocatechuic acid: the missing human cyanidins' metabolite. Mol. Nutr. Food Res., 2008, 52, 386-387.
100. Galvano, F.; La Fauci, L.; Lazzarino, G.; Fogliano, V.; Ritieni, A.; Cappellano, S.; Battistini, N.C.; Tavazzi, B.; Galvano, G. Cyanidins: metabolism and biological properties. J. Nutr. Biochem., 2004, 14, 2-11.