Inhibition of ErbB receptors, Hedgehog and NF-kappaB signaling by polyphenols in cancer

Frontiers in Bioscience

Volumn 18, Issue 4, 2013, Pages 1290-1310

  Benvenuto, Monica ^a   Fantini, Massimo ^a   Masuelli, Laura ^b   Smaele, Enrico De ^b   Zazzeroni, Francesca ^c   Tresoldi, Ilaria ^a   Calabrese, Giorgio ^d   Galvano, Fabio ^e   Modesti, Andrea ^a   Bei, Roberto ^a  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

^c UNIVERSITY OF L'AQUILA   (Italy)

^d UNIVERSITY OF EASTERN PIEDMONT   (Italy)

^e UNIVERSITY OF CATANIA   (Italy)

Author keywords

Cancer; ErbB receptor; Hedgehog; NF kappaB; Polyphenols; Review

Indexed keywords

EID: 84880529305     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/4180     Document Type: Article

References (166)

1. J.S. Bertram: The molecular biology of cancer. Mol Aspects Med 21, 167-223 (2000). (Pubitemid 32118230)
2. D. Hanahan, R.A. Weinberg: The hallmarks of cancer. Cell 100, 57-70 (2000). (Pubitemid 30046295)
3. R. Bei, L. Masuelli, M. Turriziani, G. Li Volti, M. Malaguarnera, F. Galvano: Impaired expression and function of signaling pathway enzymes by anthocyanins: role on cancer prevention and progression. Curr Enzyme Inhib 5, 184-197 (2009).
4. R. Bei, C. Palumbo, L. Masuelli, M. Turriziani, G.V. Frajese, G. Li Volti, M. Malaguarnera, F. Galvano: Impaired expression and function of cancer-related enzymes by anthocyans: an update. Curr Enzyme Inhib 8, 2-21 (2012).
5. A.B. Kunnumakkara, P. Anand, B.B. Aggarwal: Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett 269, 199-225 (2008).
6. L. Marzocchella, M. Fantini, M. Benvenuto, L. Masuelli, I. Tresoldi, A. Modesti, R. Bei: Dietary flavonoids: molecular mechanisms of action as anti-inflammatory agents. Recent Pat Inflamm Allergy Drug Discov 5, 200-220 (2011).
7. V. Izzi, L. Masuelli, I. Tresoldi, P. Sacchetti, A. Modesti, F. Galvano, R. Bei: The effects of dietary flavonoids on the regulation of redox inflammatory networks. Front Biosci 17, 2396-2418 (2012).
8. Y. Yarden, M.X. Sliwkowsky: Untangling the ErbB signaling network. Nat Rev Mol Cell Biol 2, 127-137 (2001).
9. K.L. Carraway 3rd, L.C. Cantley: A neu acquaintance for erbB3 and erbB4: a role for receptor heterodimerization in growth signaling. Cell 78, 5-8 (1994).
10. M.M. McKay, D.K. Morrison: Integrating signals from RTKs to ERK/MAPK. Oncogene 26, 3113-3121 (2007). (Pubitemid 46763008)
11. N. Normanno, C. Bianco, A. De Luca, M.R. Maiello, D.S. Salomon: Target-based agents against ErbB receptors and their ligands: a novel approach to cancer treatment. Endocr Relat Cancer 10, 1-21 (2003). (Pubitemid 36457237)
12. L. Masuelli, L. Marzocchella, A. Quaranta, C. Palumbo, G. Pompa, V. Izzi, A. Canini, A. Modesti, F. Galvano, R. Bei: Apigenin induces apoptosis and impairs head and neck carcinomas EGFR/ErbB2 signaling. Front Biosci 16, 1060-1068 (2011).
13. C. Palumbo, R. Bei, A. Procopio, A. Modesti: Molecular targets and targeted therapies for malignant mesothelioma. Curr Med Chem 15, 855-867 (2008). (Pubitemid 351736408)
14. D. Alesiani, R. Cicconi, M. Mattei, R. Bei, A. Canini: Inhibition of Mek 1/2 kinase activity and stimulation of melanogenesis by 5, 7-dimethoxycoumarin treatment of melanoma cells. Int J Oncol 34, 1727-1735 (2009).
15. M. Renis, L. Calandra, C. Scifo, B. Tomasello, V. Cardile, L. Vanella, R. Bei, L. La Fauci, F. Galvano: Response of cell cycle/stress-related protein expression and DNA damage upon treatment of CaCo2 cells with anthocyanins. Br J Nutr 100, 27-35 (2008).
16. L. Masuelli, L. Marzocchella, C. Focaccetti, I. Tresoldi, C. Palumbo, V. Izzi, M. Benvenuto, M. Fantini, F. Lista, U. Tarantino, A. Modesti, F. Galvano, R. Bei: Resveratrol and diallyl disulfide enhance curcumin-induced sarcoma cell apoptosis. Front Biosci 17, 498-508 (2012).
17. M.L. Disis, K. Schiffman: Cancer vaccines targeting the HER2/neu oncogenic protein. Semin Oncol 28, 12-20 (2001). (Pubitemid 34062044)
18. L. Masuelli, C. Focaccetti, V. Cereda, F. Lista, D. Vitolo, P. Trono, P. Gallo, A. Amici, P. Monaci, M. Mattei, M. Modesti, G. Forni, M.H. Kraus, R. Muraro, A. Modesti, R. Bei: Gene-specific inhibition of breast carcinoma in BALB-neuT mice by active immunization with rat Neu or human ErbB receptors. Int J Oncol 30, 381-392 (2007).
19. L. Masuelli, L. Marzocchella, C. Focaccetti, F. Lista, A. Nardi, A. Scardino, M. Mattei, M. Turriziani, M. Modesti, G. Forni, J. Schlom, A. Modesti, R. Bei: Local delivery of recombinant vaccinia virus encoding for neu counteracts growth of mammary tumors more efficiently than systemic delivery in neu transgenic mice. Cancer Immunol Immunother 59, 1247-1258 (2010).
20. R. Bei, L. Masuelli, E. Moriconi, V. Visco, A. Moretti, M.H. Kraus, R. Muraro: Immune responses to all ErbB family receptors detectable in serum of cancer patients. Oncogene 18, 1267-1275 (1999). (Pubitemid 29094878)
21. R. Bei, G. Pompa, D. Vitolo, E. Moriconi, L. Ciocci, M. Quaranta, L. Frati, M.H. Kraus, R. Muraro: Colocalization of multiple ErbB receptors in stratified epithelium of oral squamous cell carcinoma. J Pathol 195, 343-348 (2001).
22. R. Bei, A. Budillon, L. Masuelli, V. Cereda, D. Vitolo, E. Di Gennaro, V. Ripavecchia, C. Palumbo, F. Ionna, S. Losito, A. Modesti, M.H. Kraus, R. Muraro: Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients. J Pathol 204, 317-325 (2004). (Pubitemid 39430092)
23. L. Masuelli, A. Budillon, L. Marzocchella, M.A. Mrozek, D. Vitolo, E. Di Gennaro, S. Losito, P. Sale, F. Longo, F. Ionna, F. Lista, R. Muraro, A. Modesti, R. Bei: Caveolin-1 overexpression is associated with simultaneous abnormal expression of the E-cadherin/α-β catenins complex and multiple ErbB receptors and with lymph nodes metastasis in head and neck squamous cell carcinomas. J Cell Physiol 227, 3344-3353 (2012).
24. R. Bei, L. Masuelli, C. Palumbo, M. Modesti, A. Modesti: A common repertoire of autoantibodies is shared by cancer and autoimmune disease patients: Inflammation in their induction and impact on tumor growth. Cancer Lett 281, 8-23 (2009).
25. A. Scardino, M. Alimandi, P. Correale, S.G. Smith, R. Bei, H. Firat, M.G. Cusi, O. Faure, S. Graf-Dubois, G. Cencioni, J. Marrocco, S. Chouaib, F.A. Lemonnier, A.M. Jackson, K. Kosmatopoulos: A polyepitope DNA vaccine targeted to Her-2/ErbB-2 elicits a broad range of human and murine CTL effectors to protect against tumor challenge. Cancer Res 67, 7028-7036 (2007). (Pubitemid 47105552)
26. G. Ingrosso, M. Fantini, A. Nardi, M. Benvenuto, P. Sacchetti, L. Masuelli, E. Ponti, G.V. Frajese, F. Lista, O. Schillaci, R. Santoni, A. Modesti, R. Bei: Local radiotherapy increases the level of autoantibodies to ribosomal P0 protein but not to heat shock proteins, extracellular matrix molecules and EGFR/ErbB2 receptors in prostate cancer patients. Oncol Rep 29, 1167-1174 (2013).
27. V. Visco, R. Bei, E. Moriconi, W. Gianni, M.H. Kraus, R. Muraro: ErbB2 immune response in breast cancer patients with soluble receptor ectodomain. Am J Pathol 156, 1417-1424 (2000). (Pubitemid 30662076)
28. S. Rovero, A. Amici, E. Di Carlo, R. Bei, P. Nanni, E. Quaglino, P. Porcedda, K. Boggio, A. Smorlesi, P.L. Lollini, L. Landuzzi, M.P. Colombo, M. Giovarelli, P. Musiani, G. Forni: DNA vaccination against rat her-2/Neu p185 more effectively inhibits carcinogenesis than transplantable carcinomas in transgenic BALB/c mice. J Immunol 165, 5133-5142 (2000).
29. F.H. Sarkar, Y. Li, Z. Wang, D. Kong: NF-kappaB signaling pathway and its therapeutic implications in human diseases. Int Rev Immunol 27, 293-319 (2008).
30. W.E. Naugler, M. Karin: NF-kappaB and canceridentifying targets and mechanisms. Curr Opin Genet Dev 18, 19-26 (2008).
31. D.K. Biswas, J.D. Iglehart: Linkage between EGFR family receptors and nuclear factor kappaB (NF-kappaB) signaling in breast cancer. J Cell Physiol 209, 645-652 (2006). (Pubitemid 44665682)
32. A. Sica, P. Allavena, A. Mantovani: Cancer related inflammation: the macrophage connection. Cancer Lett 267, 204-215 (2008).
33. D. Wang, R.N. Dubois: Prostaglandins and cancer. Gut 55, 115-122 (2006). (Pubitemid 41820645)
34. L.F. Chen, Y. Mu, W.C. Greene: Acetylation of RelA at discrete sites regulates distinct nuclear functions of NFkappaB. EMBO J 21, 6539-6548 (2002). (Pubitemid 35448431)
35. L.F. Chen, W.C. Greene: Assessing acetylation of NFkappaB. Methods 36, 368-375 (2005).
36. M. Mimeault, S.L. Johansson, J.P. Henichart, P. Depreux, S.K. Batra: Cytotoxic effects induced by docetaxel, gefitinib, and cyclopamine on side population and nonside population cell fractions from human invasive prostate cancer cells. Mol Cancer Ther 9, 617-630 (2010).
37. D. Mangelberger, D. Kern, A. Loipetzberger, M. Eberl, F. Aberger: Cooperative Hedgehog-EGFR signaling. Front Biosci 17, 90-99 (2012).
38. S. Teglund, R. Toftgård: Hedgehog beyond medulloblastoma and basal cell carcinoma. Biochim Biophys Acta 1805, 181-208 (2010).
39. L. Masuelli, R. Bei, P. Sacchetti, I. Scappaticci, P. Francalanci, L. Albonici, A. Coletti, C. Palumbo, M. Minieri, R. Fiaccavento, F. Carotenuto, C. Fantini, L. Carosella, A. Modesti, P. Di Nardo: Beta-catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts. Cardiovasc Res 60, 376-387 (2003). (Pubitemid 37412371)
40. M. Kubo, M. Nakamura, A. Tasaki, N. Yamanaka, H. Nakashima, M. Nomura, S. Kuroki, M. Katano: Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res 64, 6071-6074 (2004). (Pubitemid 39129406)
41. W. Cui, L.H. Wang, Y.Y.Wen, M. Song, B.L. Li, X.L. Chen, M. Xu, S.X. An, J. Zhao, Y.Y. Lu, X.Y. Mi, E.H. Wang: Expression and regulation mechanisms of Sonic Hedgehog in breast cancer. Cancer Sci 101, 927-933 (2010).
42. S. Peukert, K. Miller-Moslin: Small-molecule inhibitors of the hedgehog signaling pathway as cancer therapeutics. Chem Med Chem 5, 500-512 (2010).
43. M. Kasper, H. Schnidar, G.W. Neill, M. Hanneder, S. Klingler, L. Blaas, C. Schmid, C. Hauser-Kronberger, G. Regl, M.P. Philpott, F. Aberger: Selective modulation of Hedgehog/GLI target gene expression by epidermal growth factor signaling in human keratinocytes. Mol Cell Biol 26, 6283-6298 (2006). (Pubitemid 44204544)
44. R.L. Bigelow, E.Y. Jen, M. Delehedde, N.S. Chari, T.J. McDonnell: Sonic hedgehog induces epidermal growth factor dependent matrix infiltration in HaCaT keratinocytes. J Invest Dermatol 124, 457-465 (2005). (Pubitemid 40175896)
45. M. Eberl, S. Klingler, D. Mangelberger, A. Loipetzberger, H. Damhofer, K. Zoidl, H. Schnidar, H. Hache, H.C. Bauer, F. Solca, C. Hauser-Kronberger, A.N. Ermilov, M.E. Verhaegen, C.K. Bichakjian, A.A Dlugosz, W. Nietfeld, M. Sibilia, H. Lehrach, C. Wierling, F. Aberger: Hedgehog-EGFR cooperation response genes determine the oncogenic phenotype of basal cell carcinoma and tumour-initiating pancreatic cancer cells. EMBO Mol Med 4, 218-233 (2012).
46. B. Stecca, C. Mas, V. Clement, M. Zbinden, R. Correa, V. Piguet, F. Beermann, A. Ruiz I Altaba: Melanomas require HEDGEHOG-GLI signaling regulated by interactions between GLI1 and the RAS-MEK/AKT pathways. Proc Natl Acad Sci U S A 104, 5895-5900 (2007). (Pubitemid 47175630)
47. N.A. Riobó, K. Lu, X. Ai, G.M. Haines, C.P. Jr Emerson: Phosphoinositide 3-kinase and Akt are essential for Sonic Hedgehog signaling. Proc Natl Acad Sci U S A 103, 4505-4510 (2006).
48. N.A. Riobó, G.M. Haines, C.P. Jr Emerson: Protein kinase C-delta and mitogen-activated protein/extracellular signal-regulated kinase-1 control GLI activation in hedgehog signaling. Cancer Res 66, 839-845 (2006). (Pubitemid 43165949)
49. H. Schnidar, M. Eberl, S. Klingler, D. Mangelberger, M. Kasper, C. Hauser-Kronberger, G. Regl, R. Kroismayr, R. Moriggl, M. Sibilia, F. Aberger: Epidermal growth factor receptor signaling synergizes with Hedgehog/GLI in oncogenic transformation via activation of the MEK/ERK/JUN pathway. Cancer Res 69, 1284-1292 (2009).
50. M. Seto, M. Ohta, Y. Asaoka, T. Ikenoue, M. Tada, K. Miyabayashi, D. Mohri, Y. Tanaka, H. Ijichi, K. Tateishi, F. Kanai, T. Kawabe, M. Omata: Regulation of the hedgehog signaling by the mitogen-activated protein kinase cascade in gastric cancer. Mol Carcinog 48, 703-712 (2009).
51. G. Shaw, D.M. Prowse: Inhibition of androgenindependent prostate cancer cell growth is enhanced by combination therapy targeting Hedgehog and ErbB signalling. Cancer Cell Int 8, 3 (2008).
52. K. Hinohara, S. Kobayashi, H. Kanauchi, S. Shimizu, K. Nishioka, E. Tsuji, K. Tada, K. Umezawa, M. Mori, T. Ogawa, J. Inoue, A. Tojo, N. Gotoh: ErbB receptor tyrosine kinase/NF-κB signaling controls mammosphere formation in human breast cancer. Proc Natl Acad Sci U S A 109, 6584-6589 (2012).
53. E.C. Merkhofer, P. Cogswell, A.S. Baldwin: Her2 activates NF-kappaB and induces invasion through the canonical pathway involving IKKalpha. Oncogene 29, 1238-1248 (2010).
54. M.A. Rivas, M. Tkach, W. Beguelin, C.J. Proietti, C. Rosemblit, E.H. Charreau, P.V. Elizalde, R. Schillaci: Transactivation of ErbB-2 induced by tumor necrosis factor alpha promotes NF-kappaB activation and breast cancer cell proliferation. Breast Cancer Res Treat 122, 111-124 (2010).
55. M. Liu, X. Ju, N.E. Willmarth, M.C. Casimiro, J. Ojeifo, T. Sakamaki, S. Katiyar, X. Jiao, V.M. Popov, Z.Yu, K. Wu, D. Joyce, C. Wang, R.G. Pestell: Nuclear factor-kappaB enhances ErbB2-induced mammary tumorigenesis and neoangiogenesis in vivo. Am J Pathol 174, 1910-1920 (2009).
56. Y. Cao, J.L. Luo, M. Karin: IkappaB kinase alpha kinase activity is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells. Proc Natl Acad Sci U S A 104, 15852-15857 (2007). (Pubitemid 350035388)
57. D.K. Biswas, Q. Shi, S. Baily, I. Strickland, S. Ghosh, A.B. Pardee, J.D. Iglehart: NF-kB activation in human breast cancer specimens and its role in cell proliferation and apoptosis. Proc Natl Acad Sci U S A 101, 10137-10142 (2004). (Pubitemid 38891208)
58. C. Le Page, I.H. Koumakpayi, L. Lessard, A.M. Mes-Masson, F. Saad: EGFR and Her-2 regulate the constitutive activation of NF-kappaB in PC-3 prostate cancer cells. Prostate 65, 130-140 (2005). (Pubitemid 41362280)
59. S. Pianetti, M. Arsura, R. Romieu-Mourez, R.J. Coffey, G.E. Sonenshein: Her-2/neu overexpression induces NFkappaB via a PI3-kinase/Akt pathway involving calpainmediated degradation of IkappaB-alpha that can be inhibited by the tumor suppressor PTEN. Oncogene 20, 1287-1299 (2001). (Pubitemid 32269934)
60. K. Makino, C.P. Day, S.C. Wang, Y.M. Li, M.C. Hung: Upregulation of IKKalpha/IKKbeta by integrin-linked kinase is required for HER2/neu-induced NF-kappaB antiapoptotic pathway. Oncogene 23, 3883-3887 (2004). (Pubitemid 38725701)
61. B.P. Zhou, M.C. Hu, S.A. Miller, Z. Yu, W. Xia, S.Y. Lin, M.C. Hung: HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway. J Biol Chem 275, 8027-8031 (2000). (Pubitemid 30159714)
62. B. Poligone, A.S. Baldwin: Positive and negative regulation of NF-kappaB by COX-2: roles of different prostaglandins. J Biol Chem 276, 38658-38664 (2001).
63. H. Nakashima, M. Nakamura, H. Yamaguchi, N. Yamanaka, T. Akiyoshi, K. Koga, K. Yamaguchi, M. Tsuneyoshi, M. Tanaka, M. Katano: Nuclear factor-kappaB contributes to hedgehog signaling pathway activation through sonic hedgehog induction in pancreatic cancer. Cancer Res 66, 7041-7049 (2006). (Pubitemid 44197680)
64. H. Kasperczyk, B. Baumann, K.M. Debatin, S. Fulda: Characterization of sonic hedgehog as a novel NF-kappaB target gene that promotes NF-kappaB-mediated apoptosis resistance and tumor growth in vivo. FASEB J 23, 21-33 (2009).
65. S.Scalbert, G. Williamson: Dietary intake and bioavailability of polyphenols. J Nutr 130, 20173S-2085S (2000).
66. C. Manach, A. Scalbert, C. Morand, C. Rémésy, L. Jiménez: Polyphenols: Food sources and bioavailability. Am J Clin Nutr 79, 727-747 (2004). (Pubitemid 41103873)
67. A. Crozier, I.B. Jaganath, M.N. Clifford: Dietary phenolics: Chemistry, bioavailability and effects on health. Nat Prod Rep 26, 1001-1043 (2009).
68. S. Pianetti, S. Guo, K.T. Kavanagh, G.E. Sonenshein: Green tea polyphenol epigallocatechin-3 gallate inhibits Her-2/neu signaling, proliferation, and transformed phenotype of breast cancer cells. Cancer Res 62, 652-655 (2002). (Pubitemid 34126935)
69. M.H. Pan, C.C. Lin, J.K. Lin, W.J. Chen: Tea polyphenol (-)-epigallocatechin 3-gallate suppresses heregulin-beta1-induced fatty acid synthase expression in human breast cancer cells by inhibiting phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase cascade signaling. J Agric Food Chem 55, 5030-5037 (2007).
70. M. Masuda, M. Suzui, J.T. Lim, A. Deguchi, J.W. Soh., I.B. Weinstein: Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction. J Exp Ther Oncol 2, 350-359 (2002). (Pubitemid 35265984)
71. M. Masuda, M. Suzui, J.T. Lim, I.B. Weinstein: Epigallocatechin-3-gallate inhibits activation of HER-2/neu and downstream signaling pathways in human head and neck and breast carcinoma cells. Clin Cancer Res 9, 3486-3491 (2003). (Pubitemid 37082748)
72. C.M. Chang, P.Y. Chang, M.G. Tu, C.C. Lu, S.C. Kuo, S. Amagaya, C.Y. Lee, H.Y. Jao, M.Y. Chen, J.S. Yang: 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 28, 1799-1807 (2012).
73. S.F. Eddy, S.E. Kane, G.E. Sonenshein: Trastuzumabresistant HER2-driven breast cancer cells are sensitive to epigallocatechin-3 gallate. Cancer Res 67, 9018-9123 (2007).
74. S. Guo, J. Lu, A. Subramanian, G.E. Sonenshein: Microarray-assisted pathway analysis identifies mitogenactivated protein kinase signaling as a mediator of resistance to the green tea polyphenol epigallocatechin 3-gallate in her-2/neu-overexpressing breast cancer cells. Cancer Res 66, 5322-5329 (2006). (Pubitemid 43844957)
75. Z. Hou, S. Sang, H. You, M.J. Lee, J. Hong, K.V. Chin, C.S. Yang: Mechanism of action of (-)-epigallocatechin-3-gallate: auto-oxidation-dependent inactivation of epidermal growth factor receptor and direct effects on growth inhibition in human esophageal cancer KYSE 150 cells. Cancer Res 65, 8049-8056 (2005). (Pubitemid 41297287)
76. M. Shimizu, A. Deguchi, A.K. Joe, J.F. Mckoy, H. Moriwaki, I.B. Weinstein: EGCG inhibits activation of HER3 and expression of cyclooxygenase-2 in human colon cancer cells. J Exp Ther Oncol 5, 69-78 (2005). (Pubitemid 41076992)
77. S. Adachi, T. Nagao, H.I. Ingolfsson, F.R. Maxfield, O.S. Andersen, L. Kopelovich, I.B. Weinstein: The inhibitory effect of (-)-epigallocatechin gallate on activation of the epidermal growth factor receptor is associated with altered lipid order in HT29 colon cancer cells. Cancer Res 67, 6493-6501 (2007). (Pubitemid 47037535)
78. S. Adachi, T. Nagao, S. To, A.K. Joe, M. Shimizu, R. Matsushima- Nishiwaki, O. Kozawa, H. Moriwaki, F.R. Maxfield, I.B. Weinstein: (-)-Epigallocatechin gallate causes internalization of the epidermal growth factor receptor in human colon cancer cells. Carcinogenesis 29, 1986-1993 (2008).
79. S. Adachi, M. Shimizu, Y. Shirakami, J. Yamauchi, H. Natsume, R. Matsushima-Nishiwaki, S. To, I.B. Weinstein, H. Moriwaki, O. Kozawa: (-)-Epigallocatechin gallate downregulates EGF receptor via phosphorylation at Ser1046/1047 by p38 MAPK in colon cancer cells. Carcinogenesis 30, 1544-1552 (2009).
80. S.A. Milligan, P. Burke, D.T. Coleman, R.L. Bigelow, J.J. Steffan, J.L. Carroll, B.J. Williams, J.A. Cardelli: The green tea polyphenol EGCG potentiates the antiproliferative activity of c-Met and epidermal growth factor receptor inhibitors in non-small cell lung cancer cells. Clin Cancer Res 15, 4885-4894 (2009).
81. S.M. Gadgeel, S. Ali, P.A. Philip, A. Wozniak, F.H. Sarkar: Genistein enhances the effect of epidermal growth factor receptor tyrosine kinase inhibitors and inhibits nuclear factor kappa B in nonsmall cell lung cancer cell lines. Cancer 115, 2165-76 (2009).
82. D. Fridrich, N. Teller, M. Esselen, G. Pahlke, D. Marko: Comparison of delphinidin, quercetin and (-)-epigallocatechin-3-gallate as inhibitors of the EGFR and the ErbB2 receptor phosphorylation. Mol Nutr Food Res 52, 815-822 (2008).
83. F. Afaq, N. Zaman, N. Khan, D.N. Syed, S. Sarfaraz, M.A. Zaid, H. Mukhtar: Inhibition of epidermal growth factor receptor signaling pathway by delphinidin, an anthocyanidin in pigmented fruits and vegetables. Int J Cancer 123, 1508-1515 (2008).
84. N. Teller, W. Thiele, U. Boettler, J. Sleeman, D. Marko: Delphinidin inhibits a broad spectrum of receptor tyrosine kinases of the ErbB and VEGFR family. Mol Nutr Food Res 53, 1075-1083 (2009).
85. T. Ozbay, R. Nahta: Delphinidin inhibits HER2 and Erk1/2 signaling and suppresses growth of HER2-overexpressing and triple negative breast cancer cell lines. Breast Cancer (Auckl) 5, 143 (2011).
86. M. Xu, K.A. Bower, G. Chen, X. Shi, Z. Dong, Z. Ke, J. Luo: Ethanol enhances the interaction of breast cancer cells over-expressing ErbB2 with fibronectin. Alcohol Clin Exp Res 34, 751-60 (2010).
87. E.J. Lee, S.Y. Oh, M.K. Sung: Luteolin exerts antitumor activity through the suppression of epidermal growth factor receptor-mediated pathway in MDA-MB-231 ERnegative breast cancer cells. Food Chem Toxicol 50, 4136-4143 (2012).
88. E.B. Yang, L. Wei, K. Zhang, Y.Z. Chen, W.N. Chen: Tannic Acid, a Potent Inhibitor of Epidermal Growth Factor Receptor Tyrosine Kinase. J Biochem 139, 495-502 (2006). (Pubitemid 43667113)
89. M. Katdare, M. Osborne, N.T. Telang: Soy isoflavone genistein modulates cell cycle progression and induce apoptosis in HER-2/neu oncogene expressing human breast epithelial cells. Int J Oncol 21, 809-815 (2002).
90. M.S. Sakla, N.S. Shenouda, P.J. Ansell, R.S. Macdonald, D.B. Lubahn: Genistein affects HER2 protein concentration, activation, and promoter regulation in BT-474 human breast cancer cells. Endocrine 32, 69-78 (2007). (Pubitemid 350242549)
91. D. Fridrich, A. Glabasnia, J. Fritz, M. Esselen, G. Pahlke, T. Hofmann, D. Marko: Oak ellagitannins suppress the phosphorylation of the epidermal growth factor receptor in human colon carcinoma cells. J Agric Food Chem 56, 3010-3015 (2008). (Pubitemid 351746022)
92. D. Fridrich, M. Kern, J. Fritz, G. Pahlke, N. Kohler, P. Winterhalter, D. Marko: The epidermal growth factor receptor and human topoisomerases represent potential cellular targets of oligomeric procyanidins. Mol Nutr Food Res 51, 192-200 (2007). (Pubitemid 47083250)
93. J.H. Jeong, J.Y. An, Y.T. Kwon, L.Y. Li, Y.J. Lee: Quercetin induced ubiquitination and down regulation of Her 2/neu. J Cell Biochem 105, 585-595 (2008).
94. J.A. Menendez, A. Vazquez-Martin, R. Garcia-Villalba, A. Carrasco-Pancorbo, C. Oliveras-Ferraros, A. Fernandez-Gutierrez, A. Segura-Carretero: tabAnti-HER2 (erbB-2) oncogene effects of phenolic compounds directly isolated from commercial Extra-Virgin Olive Oil (EVOO). BMC Cancer 8, 377 (2008).
95. J.A. Menendez, A. Vazquez-Martin, C. Oliveras-Ferraros, R. Garcia-Villalba, A. Carrasco-Pancorbo, A. Fernandez-Gutierrez, A. Segura-Carretero: 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 34, 43-51 (2009).
96. C. Oliveras-Ferraros, S. Fernández-Arroyo, A. Vazquez-Martin, J. Lozano-Sánchez, S. Cufí, J. Joven, V. Micol, A. Fernández-Gutiérrez, A. Segura-Carretero, J.A. Menendez: 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 38, 1533-1547 (2011).
97. R.L. Hong, W.H. Spohn, M.C. Hung: Curcumin inhibits tyrosine kinase activity of p185neu and also depletes p185neu. Clin Cancer Res 5, 1884-1891 (1999). (Pubitemid 29334473)
98. Y. Jung, W. Xu, H. Kim, N. Ha, L. Neckers: Curcumininduced degradation of ErbB2: A role for the E3 ubiquitin ligase CHIP and the Michael reaction acceptor activity of curcumin. Biochim Biophys Acta 1773, 383-390 (2007). (Pubitemid 46275067)
99. M.S. Squires, E.A. Hudson, L. Howells, S. Sale, C.E. Houghton, J.L. Jones, L.H. Fox, M. Dickens, S.A. Prigent, M.M. Manson: Relevance of mitogen activated protein kinase (MAPK) and phosphotidylinositol-3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin in breast cells. Biochem Pharmacol 65, 361-376 (2003). (Pubitemid 36084553)
100. X.D. Sun, X.E. Liu, D.S. Huang: Curcumin induces apoptosis of triple-negative breast cancer cells by inhibition of EGFR expression. Mol Med Report 6, 1267-1270 (2012).
101. T.J. Somers-Edgar, M.J. Scandlyn, E.C. Stuart, M.J. Le Nedelec, S.P. Valentine, R.J. Rosengren: The combination of epigallocatechin gallate and curcumin suppresses ER alpha-breast cancer cell growth in vitro and in vivo. Int J Cancer 122, 1966-1971 (2008). (Pubitemid 351441184)
102. S.H. Sun, H.C. Huang, C. Huang, J.K. Lin: Cycle arrest and apoptosis in MDA-MB-231/Her2 cells induced by curcumin. Eur J Pharmacol 690, 22-30 (2012).
103. H.W. Lai, S.Y. Chien, S.J. Kuo, L.M. Tseng, H.Y. Lin, C.W. Chi, D.R. Chen: The potential utility of curcumin in the treatment of HER-2-overexpressed breast cancer: an in vitro and in vivo comparison study with Herceptin. Evid Based Complement Alternat Med 2012, 486568 (2012).
104. X.Z. Cai, J. Wang, X.D. Li, G.L. Wang, F.N. Liu, M.S. Cheng, F. Li: Curcumin suppresses proliferation and invasion in human gastric cancer cells by downregulation of PAK1 activity and cyclin D1 expression. Cancer Biol Ther 8, 1360-1368 (2009).
105. A.P. Majumdar, S. Banerjee, J. Nautiyal, B.B. Patel, V. Patel, J. Du, Y. Yu, A.A. Elliott, E. Levi, F.H. Sarkar: Curcumin synergizes with resveratrol to inhibit colon cancer. Nutr Cancer 61, 544-553 (2009).
106. J. Nautiyal, S. Banerjee, S.S. Kanwar, Y. Yu, B.B. Patel, F.H. Sarkar, A.P. Majumdar: Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells. Int J Cancer 128, 951-961 (2011).
107. B.B. Patel, R. Sengupta, S. Qazi, H. Vachhani, Y. Yu, A.K. Rishi, A.P. Majumdar: Curcumin enhances the effects of 5-fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF-1R. Int J Cancer 122, 267-273 (2008). (Pubitemid 350234711)
108. B.B. Patel, D. Gupta, A.A. Elliott, V. Sengupta, Y. Yu, A.P. Majumdar: Curcumin targets FOLFOX-surviving colon cancer cells via inhibition of EGFRs and IGF-1R. Anticancer Res 30, 319-325 (2010).
109. G. Chadalapaka, I. Jutooru, R. Burghardt, S. Safe: Drugs that target specificity proteins downregulate epidermal growth factor receptor in bladder cancer cells. Mol Cancer Res 8, 739-750 (2010).
110. R.L. Thangapazham, S. Shaheduzzaman, K.H. Kim, N. Passi, A. Tadese, M. Vahey, A. Dobi, S. Srivastava, R.K. Maheshwari: Androgen responsive and refractory prostate cancer cells exhibit distinct curcumin regulated transcriptome. Cancer Biol Ther 7, 1427-1435 (2008).
111. J.H. Kim, C. Xu, Y.S. Keum, B. Reddy, A. Conney, A.N. Kong: Inhibition of EGFR signaling in human prostate cancer PC-3 cells by combination treatment with beta-phenylethyl isothiocyanate and curcumin. Carcinogenesis 27, 475-482 (2006). (Pubitemid 43372876)
112. S. Lev-Ari, A. Starr, A. Vexler, V. Karaush, V. Loew, J. Greif, E. Fenig, D. Aderka, R. Ben-Yosef: Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is associated with increased apoptosis, down-regulation of COX-2 and EGFR and inhibition of Erk1/2 activity. Anticancer Res 26, 4423-4430 (2006). (Pubitemid 46031517)
113. J.Y. Lee, Y.M. Lee, G.C. Chang, S.L. Yu, W.Y. Hsieh, J.J. Chen, H.W. Chen, P.C. Yang: Curcumin induces EGFR degradation in lung adenocarcinoma and modulates p38 activation in intestine: the versatile adjuvant for gefitinib therapy. PLoS One 6, e23756 (2011).
114. D.Y. Shin, W.S. Lee, J.N. Lu, M.H. Kang, C.H. Ryu, G.Y. Kim, H.S. Kang, S.C. Shin, Y.H. Choi: Induction of apoptosis in human colon cancer HCT-116 cells by anthocyanins through suppression of Akt and activation of p38-MAPK. Int J Oncol 35, 1499-1504 (2009).
115. M.L. Ho, P.N. Chen, S.C. Chu, D.Y. Kuo, W.H. Kuo, J.Y. Chen, Y.S. Hsieh: Peonidin 3-glucoside inhibits lung cancer metastasis by downregulation of proteinases activities and MAPK pathway. Nutr Cancer 62, 505-516 (2010).
116. A. Gopalakrishnan, C.J. Xu, S.S. Nair, C. Chen, V. Hebbar, A.N. Kong: Modulation of activator protein-1 (AP-1) and MAPK pathway by flavonoids in human prostate cancer PC3 cells. Arch Pharm Res 29, 633-644 (2006). (Pubitemid 44338461)
117. S. Shukla, S. Gupta: Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt, and loss of cyclin D1 associated retinoblastoma dephosphorylation in human prostate cancer cells. Cell Cycle 6, 1102-1114 (2007). (Pubitemid 46708584)
118. X. Long, M. Fan, R.M. Bigsby, K.P. Nephew: Apigenin inhibits antiestrogen-resistant breast cancer cell growth through estrogen receptor-alpha-dependent and estrogen receptoralpha-independent mechanisms. Mol Cancer Ther 7, 2096-2108 (2008).
119. Y.C. Hsiao, W.H. Kuo, P.N. Chen, H.R. Chang, T.H. Lin, W.E. Yang, Y.S. Hsieh, S.C. Chu: Flavanone and 2'-OH flavanone inhibit metastasis of lung cancer cells via down-regulation of proteinases activities and MAPK pathway. Chem Biol Interact 167, 193-206 (2007).
120. A.B. Granado-Serrano, M.A. Martín, L. Bravo, L. Goya, S. Ramos: Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2). J Nutr 136, 2715-2721 (2006). (Pubitemid 44771763)
121. A.B. Granado-Serrano, M.A. Martín, L. Bravo, L. Goya, S. Ramos: Quercetin modulates NF-kappa B and AP-1/JNK pathways to induce cell death in human hepatoma cells. Nutr Cancer 62, 390-401 (2010).
122. T.T.T. Nguyen, E. Tran, T.H. Nguyen, P.T. Do, T.H. Huynh, H. Huynh: The role of activated MEK-ERK pathway in quercetin-induced growth inhibition and apoptosis in A549 lung cancer cells. Carcinogenesis 25, 647-659 (2004). (Pubitemid 38618516)
123. M. Alkhalaf: Resveratrol-induced growth inhibition in MDA-MB-231 breast cancer cells is associated with mitogenactivated protein kinase signaling and protein translation. Eur J Cancer Prev 16, 334-41 (2007). (Pubitemid 47165299)
124. P. Parekh, L. Motiwale, N. Naik, K.V. Rao: Downregulation of cyclin D1 is associated with decreased levels of p38 MAP kinases, Akt/PKB and Pak1 during chemopreventive effects of resveratrol in liver cancer cells. Exp Toxicol Pathol 63, 167-173 (2011).
125. A.L. Kim, Y. Zhu, H. Zhu, L. Han, L. Kopelovich, D.R. Bickers, M. Athar: Resveratrol inhibits proliferation of human epidermoid carcinoma A431 cells by modulating MEK1 and AP-1 signalling pathways. Exp Dermatol 15, 538-546 (2006). (Pubitemid 43834489)
126. J. George, M. Singh, A.K. Srivastava, K. Bhui, P. Roy, P.K. Chaturvedi, Y. Shukla: Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53. PLoS One 6, e23395 (2011).
127. I.A. Siddiqui, V.M. Adhami, F. Afaq, N. Ahmad, H. Mukhtar: Modulation of phosphatidylinositol-3-kinase/protein kinase B-and mitogen-activated protein kinase-pathways by tea polyphenols in human prostate cancer cells. J Cell Biochem 91, 232-242 (2004).
128. S.H. Sun, H.C. Huang, C. Huang, J.K. Lin: Cycle arrest and apoptosis in MDA-MB-231/Her2 cells induced by curcumin. Eur J Pharmacol 690, 22-30 (2012).
129. J.L. Watson, A. Greenshields, R. Hill, A. Hilchie, P.W. Lee, C.A. Giacomantonio, D.W. Hoskin: Curcumin-induced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling. Mol Carcinog 49, 13-24 (2010).
130. D. Alesiani, R. Cicconi, M. Mattei, C. Montesano, R. Bei, A. Canini: Cell cycle arrest and differentiation induction by 5, 7-dimethoxycoumarin in melanoma cell lines. Int J Oncol 32, 425-434 (2008). (Pubitemid 351188309)
131. R.J. Gilbertson: Medulloblastoma: Signalling a change in treatment. Lancet oncol 5, 209-218 (2004). (Pubitemid 38391216)
132. M.H. Elamin, Z. Shinwari, S.F. Hendrayani, H. Al-Hindi, E. Al-Shail, Y. Khafaga, A. Al-Kofide, A. Aboussekhra: Curcumin inhibits the Sonic Hedgehog
133. T.D. Tiet, S. Hopyan, P. Nadesan, N. Gokgoz, R. Poon, A.C. Lin, T. Yan, I.L. Andrulis, B.A. Alman, J.S. Wunder: Constitutive Hedgehog signaling in chondrosarcoma up-regulates tumor cell proliferation. Am J Pathol 168, 321-330 (2006). (Pubitemid 43062583)
134. G.Q. Tang, T.Q. Yan, W. Guo, T.T. Ren, C.L. Peng, H. Zhao, X.C. Lu, F.L. Zhao, X. Han: (-)-Epigallocatechin-3-gallate induces apoptosis and suppresses proliferation by inhibiting the human Indian Hedgehog pathway in human chondrosarcoma cells. J Cancer Res Clin Oncol 136, 1179-1185 (2010).
135. N.S. Shenouda, C. Zhou, J.D. Browning, P.J. Ansell, M.S. Sakla, D.B. Lubahn, R.S. Macdonald: Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro. Nutr Cancer 49, 200-208 (2004). (Pubitemid 39487880)
136. A. Slusarz, N.S. Shenouda, M.S. Sakla, S.K. Drenkhahn, A.S. Narula, R.S. MacDonald, C.L. Besch-Williford, D.B. Lubahn: Common botanical compounds inhibit the hedgehog signaling pathway in prostate cancer. Cancer Res 70, 3382-3390 (2010).
137. H. Li, D.G. Tang: Prostate cancer stem cells and their potential roles in metastasis. J Surg Oncol 103, 558-562 (2011).
138. C.J. Lee, J. Dosch, D.M. Simeone: Pancreatic cancer stem cells. J Clin Oncol 26, 2806-2812 (2008).
139. L. Zhang, M. Jiao, L. Li, D. Wu, K. Wu, X. Li, G. Zhu, Q. Dang, X. Wang, J.T. Hsieh, D. He: Tumorspheres derived from prostate cancer cells possess chemoresistant and cancer stem cell properties. J Cancer Res Clin Oncol 138, 675-686 (2012).
140. S.N. Tang, C. Singh, D. Nall, D. Meeker, S. Shankar, R.K. Srivastava: The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition. J Mol Signal 5, 14 (2010).
141. R.K. Srivastava, S.N. Tang, W. Zhu, D. Meeker, S. Shankar: Sulforaphane synergizes with quercetin to inhibit self-renewal capacity of pancreatic cancer stem cells. Front Biosci (Elite Ed) 3, 515-528 (2011).
142. S.N. Tang, J. Fu, D. Nall, M. Rodova, S. Shankar, R.K. Srivastava: Inhibition of sonic hedgehog pathway and pluripotency maintaining factors regulate human pancreatic cancer stem cell characteristics. Int J Cancer 131, 30-40 (2012).
143. L. Zhang, L. Li, M. Jiao, D. Wu, K. Wu, X. Li, G. Zhu, L. Yang, X. Wang, J.T. Hsieh, D. He: Genistein inhibits the stemness properties of prostate cancer cells through targeting Hedgehog-Gli1 pathway. Cancer Lett 323, 48-57 (2012).
144. F. Colotta, P. Allavena, A. Sica, C. Garlanda, A. Mantovani: Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30, 1073-1081 (2009).
145. M. Hamalainen, R. Nieminen, P. Vuorela, M. Heinonen, E. Moilanen: Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediat Inflamm 2007, 45673 (2007).
146. C. Nicholas, S. Batra, M.A. Vargo, O.H. Voss, M.A. Gavrilin, M.D. Wewers, D.C. Guttridge, E. Grotewold, A.I.Doseff: Apigenin blocks lipopolysaccharide- induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-kappaB through the suppression of p65 phosphorylation. J Immunol 179, 7121-7127 (2007).
147. S. Puangpraphant, E.G. de Mejia: Saponins in yerba mate tea (Ilex paraguariensis A. St.-Hil) and quercetin synergistically inhibit iNOS and COX-2 in lipopolysaccharide-induced macrophages through NFkappaB pathways. J Agric Food Chem 57, 8873-8883 (2009).
148. S.Y. Cho, S.J. Park, M.J. Kwon, T.S. Jeong, S.H. Bok, W.Y. Choi, W.I. Jeong, S.Y. Ryu, S.H. Do, C.S. Lee, J.C. Song, K.S. Jeong: Quercetin suppresses proinflammatory cytokines production through MAP kinases and NFkappaB pathway in lipopolysaccharide-stimulated macrophage. Mol Cell Biochem 243, 153-160 (2003).
149. S. Gupta, K. Hastak, F. Afaq, N. Ahmad, H. Mukhtar: Essential role of caspases in epigallocatechin-3-gallatemediated inhibition of nuclear factor kappaB and induction of apoptosis. Oncogene 23, 2507-2522 (2004). (Pubitemid 38520748)
150. B. Romier, J. Van De Walle, A. During, Y. Larondelle, Y.J. Schneider: Modulation of signaling nuclear factor-kappaB activation pathway by polyphenols in human intestinal Caco-2 cells. Br J Nutr 100, 542-551 (2008).
151. M.V. Garcia-Mediavilla, I. Crespo, P.S. Collado, A. Esteller, S. Sanchez-Campos S, M.J. Tunon, J. Gonzalez-Gallego: Anti-inflammatory effect of the flavones quercetin and kaempferol in Chang Liver cells involves inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway. Eur J Pharmacol 557, 221-229 (2007). (Pubitemid 46186282)
152. H.S. Seo, H.S. Choi, H.S. Choi, Y.K. Choi, J.Y. Um, I. Choi, Y.C. Shin, S.G. Ko: Phytoestrogens induce apoptosis via extrinsic pathway, inhibiting nuclear factorkappaB signaling in HER2-overexpressing breast cancer cells. Anticancer Res 31, 3301-3313 (2011).
153. B.B. Hafeez, I.A. Siddiqui, M. Asim, A. Malik, F. Afaq, V.M. Adhami, M. Saleem, M. Din, H. Mukhtar: 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 68, 8564-8572 (2008).
154. B.B. Hafeez, M. Asim, I.A. Siddiqui, V.M. Adhami, I. Murtaza, H. Mukhta: Delphinidin, a dietary anthocyanidin in pigmented fruits and vegetables: a new weapon to blunt prostate cancer growth. Cell Cycle 7, 3320-3326 (2008).
155. J.M. Yun, F. Afaq, N. Khan, H. Mukhtar: Delphinidin, an anthocyanidin in pigmented fruits and vegetables, induces apoptosis and cell cycle arrest in human colon cancer HCT116 cells. Mol Carcinog 48, 260-270 (2009).
156. M. Ding, R. Feng, S.Y. Wang, L. Bowman, Y. Lu, Y. Qian, V. Castranova, B.H. Jiang, X. Shi: Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity. J Biol Chem 281, 17359-17368 (2006).
157. S.W. Min, S.N. Ryu, D.H. Kim: Anti-inflammatory effects of black ice, cyanidin-3-O-beta-D-glycoside, and its metabolites, cyanidin and protocatechuic acid. Int Immunopharmacol 10, 959-966 (2010).
158. Y. Zhang, F. Lian, Y. Zhu, M. Xia, Q. Wang, W. Ling, X.D. Wang: Cyanidin-3-O-beta-glucoside inhibits LPS-induced expression of inflammatory mediators through decreasing IkappaBalpha phosphorylation in THP-1 cells. Inflamm Res 59, 723-730 (2010).
159. S.S. Hecht, C. Huang, G.D. Stoner, J. Li, P.M. Kenney, S.J. Sturla, S.G. Carmella: 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 27, 1617-1626 (2006). (Pubitemid 44288051)
160. L.S. Wang, S.S. Hecht, S.G. Carmella, N. Yu, B. Larue, C. Henry, C. McIntyre, C. Rocha, J.F. Lechner, G.D. Stoner: Anthocyanins in black raspberries prevent esophageal tumors in rats. Cancer Prev Res (Phila) 2, 84-93 (2009).
161. E. Pozo-Guisado, J.M. Merino, S. Mulero-Navarro, M.J. Lorenzo-Benayas, F. Centeno, A. Alvarez-Barrientos, P.M. Fernandez-Salguero: Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspaseindependent mechanism with downregulation of Bcl-2 and NF-kappaB. Int J Cancer 115, 74-84 (2005). (Pubitemid 40559670)
162. C.S. Divya, M.R. Pillai: Antitumor action of curcumin in human papillomavirus associated cells involves downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation, and modulation of apoptosis. Mol Carcinog 45, 320-332 (2006).
163. K.S. Chun, Y.S. Keum, S.S. Han, Y.S. Song, S.H. Kim, Y.J. Surh: 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 24, 1515-1524 (2003). (Pubitemid 37160842)
164. M. Russo, C. Spagnuolo, I. Tedesco, G.L. Russo: Phytochemicals in cancer prevention and therapy: truth or dare?. Toxins (Basel) 2, 517-551 (2010).
165. J. Kanwar, M. Taskeen, I. Mohammad, C. Huo, T.H. Chan, Q.P. Dou: Recent advances on tea polyphenols. Front Biosci (Elite Ed) 4, 111-131 (2012).
166. S.C. Gupta, S. Patchva, B.B. Aggarwal: Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J 15, 195-218 (2013).