Influence of berry polyphenols on receptor signaling and cell-death pathways: Implications for breast cancer prevention

Journal of Agricultural and Food Chemistry

Volumn 60, Issue 23, 2012, Pages 5693-5708

  Aiyer, Harini S ^a   Warri, Anni M ^a   Woode, Denzel R ^b   Hilakivi Clarke, Leena ^a   Clarke, Robert ^a  

^a GEORGETOWN UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

ACI rats; apoptosis; autophagy; berries; berry polyphenols; breast cancer; cyanidin; delphinidin; ellagic acid; epidermal growth factor receptor; estrogen receptor; kaempferol; kinase signaling; quercetin; resveratrol

Indexed keywords

AUTOPHAGY; BERRIES; BREAST CANCER; CYANIDIN; DELPHINIDIN; ELLAGIC ACID; EPIDERMAL GROWTH FACTOR RECEPTORS; ESTROGEN RECEPTOR; KAEMPFEROL; POLYPHENOLS; QUERCETIN; RESVERATROL;

AMINO ACIDS; CELL DEATH; CELL PROLIFERATION; DISEASES; ENZYMES; FATTY ACIDS; PHENOLS;

FRUITS;

EPIDERMAL GROWTH FACTOR RECEPTOR; ESTROGEN RECEPTOR; POLYPHENOL;

ANIMAL; ARTICLE; BLOOD; BREAST TUMOR; CELL DEATH; CELL PROLIFERATION; CHEMISTRY; DISEASE MODEL; DRUG EFFECT; FEMALE; FRUIT; GENETICS; HUMAN; METABOLISM; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ANIMALS; BREAST NEOPLASMS; CELL DEATH; CELL LINE, TUMOR; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; FEMALE; FRUIT; HUMANS; POLYPHENOLS; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTORS, ESTROGEN; SIGNAL TRANSDUCTION;

RATTUS;

EID: 84862167763     PISSN: 00218561     EISSN: 15205118     Source Type: Journal    
DOI: 10.1021/jf204084f     Document Type: Article

References (156)

1. Hanahan, D. and Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 2011, 144, 646-674.
2. Bode, A. M. and Dong, Z. Cancer prevention research - then and now. Nat. Rev. Cancer 2009, 9, 508-516.
3. Ross, S. A. Evidence for the relationship between diet and cancer. Exp. Oncol. 2010, 32, 137-142.
4. AICR. Prevent Breast Cancer; http://preventcancer.aicr.org/site/News2? page=NewsArticle&id=16505&printer-friendly=1.
5. Lewis, N., Martinez, L. S., Freres, D. R., Schwartz, J. S., Armstrong, K., Gray, S. W., Fraze, T., Nagler, R. H., Bourgoin, A., and Hornik, R. C. Seeking cancer-related information from media and family/friends increases fruit and vegetable consumption among cancer patients. Health Commun. 2011.
6. Seeram, N. P. Berries. In Nutritional Oncology; Heber, D., Blackburn, G., Go, V., and Milner, J., Eds.; Elsevier: Amsterdam, The Netherlands, 2006; pp 615-628.
7. Veberic, R., Jakopic, J., and Stampar, F. Flavonols and anthocyanins of elderberry fruits (Sambucus nigra L.). Acta Hortic. (ISHS) 2009, 841, 611-614.
8. Wu, X., Beecher, G. R., Holden, J. M., Haytowitz, D. B., Gebhardt, S. E., and Prior, R. L. Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. J. Agric. Food Chem. 2006, 54, 4069-4075.
9. Acconcia, F. and Marino, M. The effects of 17β-estradiol in cancer are mediated by estrogen receptor signaling at the plasma membrane. Front. Physiol. 2011, 2, 30.
10. Schiff, R., Massarweh, S. A., Shou, J., Bharwani, L., Arpino, G., Rimawi, M., and Osborne, C. K. Advanced concepts in estrogen receptor biology and breast cancer endocrine resistance: implicated role of growth factor signaling and estrogen receptor coregulators. Cancer Chemother. Pharmacol. 2005, 56 (Suppl. 1), 10-20.
11. Clarke, R., Liu, M. C., Bouker, K. B., Gu, Z., Lee, R. Y., Zhu, Y., Skaar, T. C., Gomez, B., O'Brien, K., Wang, Y., and Hilakivi-Clarke, L. A. Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling. Oncogene 2003, 22, 7316-7339.
12. Hynes, N. E. and Watson, C. J. Mammary gland growth factors: roles in normal development and in cancer. Cold Spring Harbor Perspect. Biol. 2010, 2, a003186.
13. Russo, J., Hu, Y. F., Silva, I. D., and Russo, I. H. Cancer risk related to mammary gland structure and development. Microsc. Res. Technol. 2001, 52, 204-223.
14. Clarke, R., Skaar, T. C., Bouker, K. B., Davis, N., Lee, Y. R., Welch, J. N., and Leonessa, F. Molecular and pharmacological aspects of antiestrogen resistance. J. Steroid Biochem. Mol. Biol. 2001, 76, 71-84.
15. Hayashi, S. I., Eguchi, H., Tanimoto, K., Yoshida, T., Omoto, Y., Inoue, A., Yoshida, N., and Yamaguchi, Y. The expression and function of estrogen receptor alpha and beta in human breast cancer and its clinical application. Endocr. Relat. Cancer 2003, 10, 193-202.
16. Omoto, Y., Eguchi, H., Yamamoto-Yamaguchi, Y., and Hayashi, S. Estrogen receptor (ER) β1 and ERβcx/β2 inhibit ERα function differently in breast cancer cell line MCF7. Oncogene 2003, 22, 5011-5020.
17. Thomas, C. and Gustafsson, J. A. The different roles of ER subtypes in cancer biology and therapy. Nat. Rev. Cancer 2011, 11, 597-608.
18. Bowers, J. L., Tyulmenkov, V. V., Jernigan, S. C., and Klinge, C. M. Resveratrol acts as a mixed agonist/antagonist for estrogen receptors α and β. Endocrinology 2000, 141, 3657-3667.
19. Kuiper, G. G., Lemmen, J. G., Carlsson, B., Corton, J. C., Safe, S. H., van der Saag, P. T., van der Burg, B., and Gustafsson, J. A. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β. Endocrinology 1998, 139, 4252-4263.
20. Schmitt, E., Dekant, W., and Stopper, H. Assaying the estrogenicity of phytoestrogens in cells of different estrogen sensitive tissues. Toxicol. In Vitro 2001, 15, 433-439.
21. Moutsatsou, P. The spectrum of phytoestrogens in nature: our knowledge is expanding. Hormones 2007, 6, 173-193.
22. van der Woude, H., ter Veld, M. G. R., Jacobs, N., van der Saag, P. T., Murk, A. J., and Rietjens, I. M. C. M. The stimulation of cell proliferation by quercetin is mediated by the estrogen receptor. Mol. Nutr. Food Res. 2005, 49, 763-771.
23. Zoechling, A., Reiter, E., Eder, R., Wendelin, S., Liebner, F., and Jungbauer, A. The flavonoid kaempferol is responsible for the majority of estrogenic activity in red wine. Am. J. Enol. Vitic. 2009, 60, 223-232.
24. Mueller, S. O., Simon, S., Chae, K., Metzler, M., and Korach, K. S. Phytoestrogens and their human metabolites show distinct agonistic and antagonistic properties on estrogen receptor alpha (ERα) and ERbeta in human cells. Toxicol. Sci. 2004, 80, 14-25.
25. Penttinen, P., Jaehrling, J., Damdimopoulos, A. E., Inzunza, J., Lemmen, J. G., van der Saag, P., Pettersson, K., Gauglitz, G., Makela, S., and Pongratz, I. Diet-derived polyphenol metabolite enterolactone is a tissue-specific estrogen receptor activator. Endocrinology 2007, 148, 4875-4886.
26. Schmitt, E. and Stopper, H. Estrogenic activity of naturally occurring anthocyanidins. Nutr. Cancer 2001, 41, 145-149.
27. Papoutsi, Z., Kassi, E., Tsiapara, A., Fokialakis, N., Chrousos, G. P., and Moutsatsou, P. Evaluation of estrogenic/antiestrogenic activity of ellagic acid via the estrogen receptor subtypes ERα and ERβ. J. Agric. Food Chem. 2005, 53, 7715-7720.
28. Larrosa, M., Gonzalez-Sarrias, A., Garcia-Conesa, M. T., Tomas-Barberan, F. A., and Espin, J. C. Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities. J. Agric. Food Chem. 2006, 54, 1611-1620.
29. Pearce, S. T. and Jordan, V. C. The biological role of estrogen receptors α and β in cancer. Crit. Rev. Oncol. Hematol. 2004, 50, 3-22.
30. Rassi, C. M., Lieberherr, M., Chaumaz, G., Pointillart, A., and Cournot, G. Modulation of osteoclastogenesis in porcine bone marrow cultures by quercetin and rutin. Cell Tissue Res. 2005, 319, 383-393.
31. Rucinski, M., Ziolkowska, A., Hochol, A., Pucher, A., Macchi, C., Belloni, A. S., Nussdorfer, G. G., and Malendowicz, L. K. Estradiol and resveratrol stimulating effect on osteocalcin, but not osteonectin and collagen-1α gene expression in primary culture of rat calvarial osteoblast-like cells. Int. J. Mol. Med. 2006, 18, 565-570.
32. Klinge, C. M., Blankenship, K. A., Risinger, K. E., Bhatnagar, S., Noisin, E. L., Sumanasekera, W. K., Zhao, L., Brey, D. M., and Keynton, R. S. Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors α and β in endothelial cells. J. Biol. Chem. 2005, 280, 7460-7468.
33. Klinge, C. M., Risinger, K. E., Watts, M. B., Beck, V., Eder, R., and Jungbauer, A. Estrogenic activity in white and red wine extracts. J. Agric. Food Chem. 2003, 51, 1850-1857.
34. Murphy, L. C., Skliris, G. P., Rowan, B. G., Al-Dhaheri, M., Williams, C., Penner, C., Troup, S., Begic, S., Parisien, M., and Watson, P. H. The relevance of phosphorylated forms of estrogen receptor in human breast cancer in vivo. J. Steroid Biochem. Mol. Biol. 2009, 114, 90-95.
35. Wu, R. C., Smith, C. L., and O'Malley, B. W. Transcriptional regulation by steroid receptor coactivator phosphorylation. Endocr. Rev. 2005, 26, 393.
36. Shou, J., Massarweh, S., Osborne, C. K., Wakeling, A. E., Ali, S., Weiss, H., and Schiff, R. Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J. Natl. Cancer Inst. 2004, 96, 926-935.
37. Fridrich, D., Glabasnia, A., Fritz, J., Esselen, M., Pahlke, G., Hofmann, T., and Marko, D. Oak ellagitannins suppress the phosphorylation of the epidermal growth factor receptor in human colon carcinoma cells. J. Agric. Food Chem. 2008, 56, 3010-3015.
38. Meiers, S., Kemeny, M., Weyand, U., Gastpar, R., von Angerer, E., and Marko, D. The anthocyanidins cyanidin and delphinidin are potent inhibitors of the epidermal growth-factor receptor. J. Agric. Food Chem. 2001, 49, 958-962.
39. Adachi, S., Nagao, T., Ingolfsson, H. I., Maxfield, F. R., Andersen, O. S., Kopelovich, L., and Weinstein, I. B. 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. 2007, 67, 6493-6501.
40. Youdim, K. A., Martin, A., and Joseph, J. A. Incorporation of the elderberry anthocyanins by endothelial cells increases protection against oxidative stress. Free Radical Biol. Med. 2000, 29, 51-60.
41. Ozbay, T. and Nahta, R. Delphinidin inhibits HER2 and Erk1/2 signaling and suppresses growth of HER2-overexpressing and triple negative breast cancer cell lines. Breast Cancer: Basic Clin. Res. 2011, 5, 143.
42. Clarke, R., Leonessa, F., Welch, J. N., and Skaar, T. C. Cellular and molecular pharmacology of antiestrogen action and resistance. Pharmacol. Rev. 2001, 53, 25-71.
43. Okada, H. and Mak, T. W. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat. Rev. Cancer 2004, 4, 592-603.
44. Wrighton, K. H. Cell death: a new platform for death. Nat. Rev. Mol. Cell. Biol. 2011, 12, 547.
45. Gajewska, M., Sobolewska, A., Kozlowski, M., and Motyl, T. Role of autophagy in mammary gland development. J. Physiol. Pharmacol. 2008, 59 (Suppl. 9), 237-249.
46. Strange, R., Metcalfe, T., Thackray, L., and Dang, M. Apoptosis in normal and neoplastic mammary gland development. Microsc. Res. Technol. 2001, 52, 171-181.
47. Riggins, R. B., Bouton, A. H., Liu, M. C., and Clarke, R. Antiestrogens, aromatase inhibitors, and apoptosis in breast cancer. Vitam. Horm. 2005, 71, 201-237.
48. Simstein, R., Burow, M., Parker, A., Weldon, C., and Beckman, B. Apoptosis, chemoresistance, and breast cancer: insights from the MCF-7 cell model system. Exp. Biol. Med. (Maywood) 2003, 228, 995-1003.
49. Chen, N. and Karantza-Wadsworth, V. Role and regulation of autophagy in cancer. Biochim. Biophys. Acta 2009, 1793, 1516-1523.
50. Clarke, R., Shajahan, A. N., Riggins, R. B., Cho, Y., Crawford, A., Xuan, J., Wang, Y., Zwart, A., Nehra, R., and Liu, M. C. Gene network signaling in hormone responsiveness modifies apoptosis and autophagy in breast cancer cells. J. Steroid Biochem. Mol. Biol. 2009, 114, 8-20.
51. Cook, K. L., Shajahan, A. N., and Clarke, R. Autophagy and endocrine resistance in breast cancer. Exp. Rev. Anticancer Ther. 2011, 11, 1283-1294.
52. Crawford, A. C., Riggins, R. B., Shajahan, A. N., Zwart, A., and Clarke, R. Co-inhibition of BCL-W and BCL2 restores antiestrogen sensitivity through BECN1 and promotes an autophagy-associated necrosis. PLoS One 2010, 5, e8604.
53. Grant, S. Cotargeting survival signaling pathways in cancer. J. Clin. Invest. 2008, 118, 3003-3006.
54. Yeh, C. T. and Yen, G. C. Induction of apoptosis by the anthocyanidins through regulation of Bcl-2 gene and activation of c-Jun N-terminal kinase cascade in hepatoma cells. J. Agric. Food Chem. 2005, 53, 1740-1749.
55. Kim, B. W., Lee, E. R., Min, H. M., Jeong, H. S., Ahn, J. Y., Kim, J. H., Choi, H. Y., Choi, H., Kim, E. Y., Park, S. P., and Cho, S. G. Sustained ERK activation is involved in the kaempferol-induced apoptosis of breast cancer cells and is more evident under 3-D culture condition. Cancer Biol. Ther. 2008, 7, 1080-1089.
56. Nguyen, T. H., Mustafa, F. B., Pervaiz, S., Ng, F. S., and Lim, L. H. ERK1/2 activation is required for resveratrol-induced apoptosis in MDA-MB-231 cells. Int. J. Oncol. 2008, 33, 81-92.
57. Schoenlein, P. V., Periyasamy-Thandavan, S., Samaddar, J. S., Jackson, W. H., and Barrett, J. T. Autophagy facilitates the progression of ERα-positive breast cancer cells to antiestrogen resistance. Autophagy 2009, 5, 400-403.
58. Feng, R., Wang, S. Y., Shi, Y. H., Fan, J., and Yin, X. M. Delphinidin induces necrosis in hepatocellular carcinoma cells in the presence of 3-methyladenine, an autophagy inhibitor. J. Agric. Food Chem. 2010, 58, 3957-3964.
59. Chen, R. J., Ho, C. T., and Wang, Y. J. Pterostilbene induces autophagy and apoptosis in sensitive and chemoresistant human bladder cancer cells. Mol. Nutr. Food Res. 2010, 54, 1819-1832.
60. Chen, L., Xiao, Z., Meng, Y., Zhao, Y., Han, J., Su, G., Chen, B., and Dai, J. The enhancement of cancer stem cell properties of MCF-7 cells in 3D collagen scaffolds for modeling of cancer and anti-cancer drugs. Biomaterials 2012, 33, 1437-1444.
61. Li, L. and Lu, Y. Optimizing a 3D culture system to study the interaction between epithelial breast cancer and its surrounding fibroblasts. J. Cancer 2011, 2, 458-466.
62. Rao, C. V., Tokumo, K., Rigotty, J., Zang, E., Kelloff, G., and Reddy, B. S. Chemoprevention of colon carcinogenesis by dietary administration of piroxicam, -difluoromethylornithine, 16-fluoro-5-androsten-17-one, and ellagic acid individually and in combination. Cancer Res. 1991, 51, 4528.
63. Forman, M. R., Hursting, S. D., Umar, A., and Barrett, J. C. Nutrition and cancer prevention: a multidisciplinary perspective on human trials. Annu. Rev. Nutr. 2004, 24, 223-254.
64. Cooper, D. A. Carotenoids in health and disease: recent scientific evaluations, research recommendations and the consumer. J. Nutr. 2004, 134, 221S.
65. Meyskens, F. L., Jr. and Szabo, E. Diet and cancer: the disconnect between epidemiology and randomized clinical trials. Cancer Epidemiol. Biomarkers Prev. 2005, 14, 1366-1369.
66. Block, G., Patterson, B., and Subar, A. Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr. Cancer 1992, 18, 1-29.
67. Katsube, N., Iwashita, K., Tsushida, T., Yamaki, K., and Kobori, M. Induction of apoptosis in cancer cells by bilberry (Vaccinium myrtillus) and the anthocyanins. J. Agric. Food Chem. 2003, 51, 68-75.
68. Li, L., Adams, L. S., Chen, S., Killian, C., Ahmed, A., and Seeram, N. P. Eugenia jambolana Lam. berry extract inhibits growth and induces apoptosis of human breast cancer but not non-tumorigenic breast cells. J. Agric. Food Chem. 2009, 57, 826-831.
69. Cai, T.; Huang, C. The effects of berry extracts on cell signaling pathways: leading to cellular transformation Berries Cancer Prevention 2011, 51-75
70. Adams, L. S.; Phung, S.; Yee, N.; Seeram, N. P.; Li, L.; Chen, S. Blueberry phytochemicals inhibit growth and metastatic potential of MDA-MB-231 breast cancer cells through modulation of the phosphatidylinositol 3-kinase pathway. Cancer Res. 2010, 70, 3594-3605.
71. Madhusoodhanan, R.; Natarajan, M.; Singh, J. V.; Jamgade, A.; Awasthi, V.; Anant, S.; Herman, T. S.; Aravindan, N. Effect of black raspberry extract in inhibiting NFκB dependent radioprotection in human breast cancer cells. Nutr. Cancer 2010, 62, 93-104.
72. Seeram, N. P.; Adams, L. S.; Hardy, M. L.; Heber, D. Total cranberry extract versus its phytochemical constituents: antiproliferative and synergistic effects against human tumor cell lines. J. Agric. Food Chem. 2004, 52, 2512-2517.
73. Seeram, N. P.; Adams, L. S.; Henning, S. M.; Niu, Y.; Zhang, Y.; Nair, M. G.; Heber, D. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J. Nutr. Biochem. 2005, 16, 360-367.
74. Wu, X.; Pittman, H. E., 3rd; McKay, S.; Prior, R. L. Aglycones and sugar moieties alter anthocyanin absorption and metabolism after berry consumption in weanling pigs. J. Nutr. 2005, 135, 2417-2424.
75. Warri, A. M.; Saarinen, N. M.; Makela, S. I. Can modulation of mammary gland development by dietary factors support breast cancer prevention? Horm. Res. 2007, 68, 247-260.
76. Aiyer, H.; Ravoori, S.; Gupta, R. Chemopreventive effects of berries and berry components in animal models: prevention of estrogen-mediated mammary tumors in ACI rats by berries. In Berries and Cancer Prevention; Stoner, G. D.; Seeram, N. P., Eds.; Springer: New York, 2011; pp 163-187.
77. Hilakivi-Clarke, L.; Cho, E.; Cabanes, A.; DeAssis, S.; Olivo, S.; Helferich, W.; Lippman, M. E.; Clarke, R. Dietary modulation of pregnancy estrogen levels and breast cancer risk among female rat offspring. Clin. Cancer Res. 2002, 8, 3601.
78. Clarke, R. Animal models of breast cancer: their diversity and role in biomedical research. Breast Cancer Res. Treat. 1996, 39, 1-6.
79. Felgines, C.; Krisa, S.; Mauray, A.; Besson, C.; Lamaison, J. L.; Scalbert, A.; Mérillon, J. M.; Texier, O. Radiolabelled cyanidin 3- O -glucoside is poorly absorbed in the mouse. Br. J. Nutr. 2010, 103, 1738-1745.
80. Talavéra, S.; Felgines, C.; Texier, O.; Besson, C.; Lamaison, J. L.; Rémésy, C. Anthocyanins are efficiently absorbed from the stomach in anesthetized rats. J. Nutr. 2003, 133, 4178.
81. 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, 3453-3457.
82. Mazur, W. M.; Uehara, M.; Wahala, K.; Adlercreutz, H. Phyto-oestrogen content of berries, and plasma concentrations and urinary excretion of enterolactone after a single strawberry-meal in human subjects. Br. J. Nutr. 2000, 83, 381-387.
83. Saarinen, N. M.; Warri, A.; Dings, R. P.; Airio, M.; Smeds, A. I.; Makela, S. Dietary lariciresinol attenuates mammary tumor growth and reduces blood vessel density in human MCF-7 breast cancer xenografts and carcinogen-induced mammary tumors in rats. Int. J. Cancer. 2008, 123, 1196-1204.
84. Saarinen, N. M.; Warri, A.; Airio, M.; Smeds, A.; Makela, S. Role of dietary lignans in the reduction of breast cancer risk. Mol. Nutr. Food Res. 2007, 51, 857-866.
85. Saarinen, N. M.; Power, K. A.; Chen, J.; Thompson, L. U. Lignans are accessible to human breast cancer xenografts in athymic mice. Nutr. Cancer 2008, 60, 245-250.
86. Verma, A. K.; Johnson, J. A.; Gould, M. N.; Tanner, M. A. Inhibition of 7,12-dimethylbenz(a)anthracene- and N -nitrosomethylurea-induced rat mammary cancer by dietary flavonol quercetin. Cancer Res. 1988, 48, 5754-5758.
87. Pereira, M. A.; Grubbs, C. J.; Barnes, L. H.; Li, H.; Olson, G. R.; Eto, I.; Juliana, M.; Whitaker, L. M.; Kelloff, G. J.; Steele, V. E.; Lubet, R. A. Effects of the phytochemicals, curcumin and quercetin, upon azoxymethane-induced colon cancer and 7,12-dimethylbenz[a]anthracene-induced mammary cancer in rats. Carcinogenesis 1996, 17, 1305-1311.
88. Singh, B.; Mense, S. M.; Bhat, N. K.; Putty, S.; Guthiel, W. A.; Remotti, F.; Bhat, H. K. Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats. Toxicol. Appl. Pharmacol. 2010, 247, 83-90.
89. Mense, S. M.; Singh, B.; Remotti, F.; Liu, X.; Bhat, H. K. Vitamin C and α-naphthoflavone prevent estrogen-induced mammary tumors and decrease oxidative stress in female ACI rats. Carcinogenesis 2009, 30, 1202-1208.
90. Hakkinen, S. H.; Karenlampi, S. O.; Heinonen, I. M.; Mykkanen, H. M.; Torronen, A. R. Content of the flavonols quercetin, myricetin, and kaempferol in 25 edible berries. J. Agric. Food Chem. 1999, 47, 2274-2279.
91. Aiyer, H. S.; Gupta, R. C. Berries and ellagic acid prevent estrogen-induced mammary tumorigenesis by modulating enzymes of estrogen metabolism. Cancer Prev. Res. (Phila.) 2010, 3, 727-737.
92. Aiyer, H. S.; Ravoori, S.; Vadhanam, M. V.; Schultz, D. J.; Gupta, R. C. Effect of dietary berries and ellagic acid on cell proliferation, estrogen-metabolizing enzymes and tumor indices in an estrogen-induced rat mammary tumor model. 2009, 50.
93. Aiyer, H. S.; Srinivasan, C.; Gupta, R. C. Dietary berries and ellagic acid diminish estrogen-mediated mammary tumorigenesis in ACI rats. Nutr. Cancer 2008, 60, 227-234.
94. Stoner, G. D. Foodstuffs for preventing cancer: the preclinical and clinical development of berries. Cancer Prev. Res. (Phila.) 2009, 2, 187-194.
95. Stoner, G. D.; Gupta, A. Etiology and chemoprevention of esophageal squamous cell carcinoma. Carcinogenesis 2001, 22, 1737-1746.
96. Stoner, G. D.; Wang, L. S.; Seguin, C.; Rocha, C.; Stoner, K.; Chiu, S.; Kinghorn, A. D. Multiple berry types prevent N -nitrosomethylbenzylamine-induced esophageal cancer in rats. Pharm. Res. 2010, 27, 1138-1145.
97. Aiyer, H. S.; Vadhanam, M. V.; Stoyanova, R.; Caprio, G. D.; Clapper, M. L.; Gupta, R. C. Dietary berries and ellagic acid prevent oxidative DNA damage and modulate expression of DNA repair genes. Int. J. Mol. Sci. 2008, 9, 327-341.
98. Kresty, L. A.; Morse, M. A.; Morgan, C.; Carlton, P. S.; Lu, J.; Gupta, A.; Blackwood, M.; Stoner, G. D. Chemoprevention of esophageal tumorigenesis by dietary administration of lyophilized black raspberries. Cancer Res. 2001, 61, 6112-6119.
99. Aiyer, H. S.; Li, Y.; Lasso, J. N.; Schiffman, S. C.; Slone, S. C.; Martin, R. C. Effect of freeze-dried berries on the development of reflux-induced esophageal adenocarcinoma. Nutr. Cancer: Int. J. 2011, in press.
100. Ravoori, S.; Vadhanam, M. V.; Sahoo, S.; Srinivasan, C.; Gupta, R. C. Mammary tumor induction in ACI rats exposed to low levels of 17β-estradiol. Int. J. Oncol. 2007, 31, 113-120.
101. Shull, J. D.; Spady, T. J.; Snyder, M. C.; Johansson, S. L.; Pennington, K. L. Ovary-intact, but not ovariectomized female ACI rats treated with 17β-estradiol rapidly develop mammary carcinoma. Carcinogenesis 1997, 18, 1595-1601.
102. Ruhlen, R. L.; Willbrand, D. M.; Besch-Williford, C. L.; Ma, L.; Shull, J. D.; Sauter, E. R. Tamoxifen induces regression of estradiol-induced mammary cancer in the ACI.COP-Ept2 rat model. Breast Cancer Res. Treat. 2009, 117, 517-524.
103. Berne, R. M.; Levy, M. N. Female reproduction. In Principles of Physiology, 2nd ed.; Berne, R. M.; Levy, M. N., Eds.; Mosby: St. Louis, MO, 1996.
104. Missmer, S. A.; Eliassen, A. H.; Barbieri, R. L.; Hankinson, S. E. Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. J. Natl. Cancer Inst. 2004, 96, 1856.
105. Walker, K.; Bratton, D. J.; Frost, C. Premenopausal endogenous oestrogen levels and breast cancer risk: a meta-analysis. Br. J. Cancer 2011, in press.
106. Aiyer, H.; Ravoori, S.; Schultz, D.; Gupta, R. C. Effect of dietary berries and ellagic acid on cell proliferation, estrogen-metabolizing enzymes and tumor indices in an estrogen-induced rat mammary tumor model. In Proceedings of the International Conference on New Developments in Drug Discovery from Natural Products and Traditional Medicines, SAS Nagar, Chadigarh, India, 2008.
107. Aiyer, H. S.; Kichambare, S.; Gupta, R. C. Prevention of oxidative DNA damage by bioactive berry components. Nutr. Cancer 2008, 60 (Suppl. 1), 36-42.
108. de Assis, S.; Warri, A.; Cruz, M. I.; Hilakivi-Clarke, L. Changes in mammary gland morphology and breast cancer risk in rats. J. Vis. Exp. 2010, not supplied.
109. Wu, X.; Rahal, O.; Kang, J.; Till, S. R.; Prior, R. L.; Simmen, R. C. In utero and lactational exposure to blueberry via maternal diet promotes mammary epithelial differentiation in prepubescent female rats. Nutr. Res. (N.Y.) 2009, 29, 802-811.
110. Adams, L. S.; Kanaya, N.; Phung, S.; Liu, Z.; Chen, S. Whole blueberry powder modulates the growth and metastasis of MDA-MB-231 triple negative breast tumors in nude mice. J. Nutr. 2011, 141, 1805-1812.
111. Singletary, E.; Lieberman, R.; Atkinson, N.; Sneige, N.; Sahin, A.; Tolley, S.; Colchin, M.; Bevers, T.; Stelling, C.; Fornage, B.; Fritsche, H.; Hittelman, W.; Kelloff, G.; Lippman, S. M. Novel translational model for breast cancer chemoprevention study: accrual to a presurgical intervention with tamoxifen and N -[4-hydroxyphenyl] retinamide. Cancer Epidemiol. Biomarkers Prev. 2000, 9, 1087-1090.
112. Hilakivi-Clarke, L.; de Assis, S. Fetal origins of breast cancer. Trends Endocrinol. Metab. 2006, 17, 340-348.
113. Hilakivi-Clarke, L.; Clarke, R.; Lippman, M. E. Perinatal factors increase breast cancer risk. Breast Cancer Res. Treat. 1994, 31, 273-284.
114. Hilakivi-Clarke, L.; Andrade, J. E.; Helferich, W. Is soy consumption good or bad for the breast? J. Nutr. 2010, 140.
115. Hilakivi-Clarke, L. Nutritional modulation of terminal end buds: its relevance to breast cancer prevention. Curr. Cancer Drug Targets 2007, 7, 465-474.
116. Warri, A.; Saarinen, N. M.; Makela, S.; Hilakivi-Clarke, L. The role of early life genistein exposures in modifying breast cancer risk. Br. J. Cancer 2008, 98, 1485-1493.
117. Paluszczak, J.; Krajka-Kuzniak, V.; Baer-Dubowska, W. The effect of dietary polyphenols on the epigenetic regulation of gene expression in MCF7 breast cancer cells. Toxicol. Lett. 2010, 192, 199-125.
118. Espin, J. C.; Garcia-Conesa, M. T.; Tomas-Barberan, F. A. Nutraceuticals: facts and fiction. Phytochemistry 2007, 68, 2986-3008.
119. Manach, C.; Williamson, G.; Morand, C.; Scalbert, A.; Rémésy, C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr. 2005, 81, 230S.
120. Allen, C.; Peden-Adams, M.; EuDaly, J.; Keil, D. Subchronic exposure to ellagic acid impairs cytotoxic T-cell function and suppresses humoral immunity in mice. Immunopharmacol. Immunotoxicol. 2003, 25, 409-422.
121. Del Rio, D.; Borges, G.; Crozier, A. Berry flavonoids and phenolics: bioavailability and evidence of protective effects. Br. J. Nutr. 2010, 104, S67-S90.
122. Seeram, N. P.; Lee, R.; Heber, D. Bioavailability of ellagic acid in human plasma after consumption of ellagitannins from pomegranate (Punica granatum L.) juice. Clin. Chim. Acta 2004, 348, 63-68.
123. Berry Health Benefits Network, http://berryhealth.fst.oregonstate.edu/.
124. Gu, L.; Kelm, M. A.; Hammerstone, J. F.; Beecher, G.; Holden, J.; Haytowitz, D.; Gebhardt, S.; Prior, R. L. Concentrations of proanthocyanidins in common foods and estimations of normal consumption. J. Nutr. 2004, 134, 613.
125. Rasmussen, S. E.; Frederiksen, H.; Struntze Krogholm, K.; Poulsen, L. Dietary proanthocyanidins: occurrence, dietary intake, bioavailability, and protection against cardiovascular disease. Mol. Nutr. Food Res. 2005, 49, 159-174.
126. Meng, X.; Maliakal, P.; Lu, H.; Lee, M. J.; Yang, C. S. Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice. J. Agric. Food Chem. 2004, 52, 935-942.
127. Rimando, A. M.; Kalt, W.; Magee, J. B.; Dewey, J.; Ballington, J. R. Resveratrol, pterostilbene, and piceatannol in Vaccinium berries. J. Agric. Food Chem. 2004, 52, 4713-4719.
128. Walle, T.; Hsieh, F.; DeLegge, M. H.; Oatis, J. E.; Walle, U. K. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab. Dispos. 2004, 32, 1377.
129. Zamora-Ros, R.; Andres-Lacueva, C.; Lamuela-Raventós, R. M.; Berenguer, T.; Jakszyn, P.; Martinez, C.; Sanchez, M. J.; Navarro, C.; Chirlaque, M. D.; Tormo, M. J. Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Br. J. Nutr. 2008, 100, 188-196.
130. de Kleijn, M. J. J.; Van der Schouw, Y. T.; Wilson, P. W. F.; Adlercreutz, H.; Mazur, W.; Grobbee, D. E.; Jacques, P. F. Intake of dietary phytoestrogens is low in postmenopausal women in the United States: The Framingham Study1-4. J. Nutr. 2001, 131, 1826.
131. Lofgren, L.; Sahlin, L.; Von Schoultz, B.; Fernstad, R.; Skoog, L.; Von Schoultz, E. Expression of sex steroid receptor subtypes in normal and malignant breast tissue - a pilot study in postmenopausal women. Acta Oncol. 2006, 45, 54-60.
132. Younes, M.; Honma, N. Estrogen receptor β. Arch. Pathol. Lab. Med. 2011, 135, 63-66.
133. Barone, I.; Brusco, L.; Fuqua, S. A. Estrogen receptor mutations and changes in downstream gene expression and signaling. Clin. Cancer Res. 2010, 16, 2702-2708.
134. Hall, J. M.; McDonnell, D. P. Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting. Mol. Interv. 2005, 5, 343-357.
135. Klinge, C. M. Estrogen receptor interaction with co-activators and co-repressors. Steroids 2000, 65, 227-251.
136. Skliris, G. P.; Nugent, Z. J.; Rowan, B. G.; Penner, C. R.; Watson, P. H.; Murphy, L. C. A phosphorylation code for oestrogen receptor-alpha predicts clinical outcome to endocrine therapy in breast cancer. Endocr. Relat. Cancer 2010, 17, 589-597.
137. Fernandes, I.; Faria, A.; Azevedo, J.; Soares, S.; Calhau, C.; De Freitas, V.; Mateus, N. Influence of anthocyanins, derivative pigments and other catechol and pyrogallol-type phenolics on breast cancer cell proliferation. J. Agric. Food Chem. 2010, 58, 3785-3792.
138. Notas, G.; Nifli, A. P.; Kampa, M.; Pelekanou, V.; Alexaki, V. I.; Theodoropoulos, P.; Vercauteren, J.; Castanas, E. Quercetin accumulates in nuclear structures and triggers specific gene expression in epithelial cells. J. Nutr. Biochem. 2011, not supplied.
139. Hung, H. Inhibition of estrogen receptor alpha expression and function in MCF 7 cells by kaempferol. J. Cell. Physiol. 2004, 198, 197-208.
140. Pozo-Guisado, E.; Merino, J. M.; Mulero-Navarro, S.; Lorenzo-Benayas, M. J.; Centeno, F.; Alvarez-Barrientos, A.; Fernandez-Salguero, P. M. Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspase-independent mechanism with downregulation of Bcl-2 and NF-κB. Int. J. Cancer 2005, 115, 74-84.
141. Xu, M.; Bower, K. A.; Wang, S.; Frank, J. A.; Chen, G.; Ding, M.; Shi, X.; Ke, Z.; Luo, J. Cyanidin-3-glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2. Mol. Cancer 2010, 9, 285.
142. 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.
143. 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.
144. Jeong, J. H.; An, J. Y.; Kwon, Y. T.; Li, L. Y.; Lee, Y. J. Quercetin induced ubiquitination and down regulation of Her 2/neu. J. Cell. Biochem. 2008, 105, 585-595.
145. Azios, N. G.; Dharmawardhane, S. F. Resveratrol and estradiol exert disparate effects on cell migration, cell surface actin structures, and focal adhesion assembly in MDA-MB-231 human breast cancer cells. Neoplasia (N.Y.) 2005, 7, 128.
146. Tang, F. Y.; Su, Y. C.; Chen, N. C.; Hsieh, H. S.; Chen, K. S. Resveratrol inhibits migration and invasion of human breast-cancer cells. Mol. Nutr. Food Res. 2008, 52, 683-691.
147. Pan, M.-H.; Lin, Y.-T.; Lin, C.-L.; Wei, C.-S.; Ho, C.-T.; Chen, W.-J. Suppression of heregulin β-1/HER2-modulated invasive and aggressive phenotype of breast carcinoma by pterostilbene via inhibition of matrix metalloproteinase-9, p38 kinase cascade and Akt activation. Evidence-Based Complement. Altern. Med. 2011, 2011.
148. 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.
149. Chen, P. N.; Chu, S. C.; Chiou, H. L.; Chiang, C. L.; Yang, S. F.; Hsieh, Y. S. Cyanidin 3-glucoside and peonidin 3-glucoside inhibit tumor cell growth and induce apoptosis in vitro and suppress tumor growth in vivo. Nutr. Cancer 2005, 53, 232-243.
150. 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-B signaling. Cancer Res. 2008, 68, 8564.
151. Chou, C. C.; Yang, J. S.; Lu, H. F.; Ip, S. W.; Lo, C.; Wu, C. C.; Lin, J. P.; Tang, N. Y.; Chung, J. G.; Chou, M. J. Quercetin-mediated cell cycle arrest and apoptosis involving activation of a caspase cascade through the mitochondrial pathway in human breast cancer MCF-7 cells. Arch. Pharmacal Res. 2010, 33, 1181-1191.
152. Seo, H. S.; Ju, J.; Jang, K.; Shin, I. Induction of apoptotic cell death by phytoestrogens by up-regulating the levels of phospho-p53 and p21 in normal and malignant estrogen receptor α-negative breast cells. Nutr. Res. (N.Y.). 2011, 31, 139-146.
153. Wang, K.; Liu, R.; Li, J.; Mao, J.; Lei, Y.; Wu, J.; Zeng, J.; Zhang, T.; Wu, H.; Chen, L. Quercetin induces protective autophagy in gastric cancer cells: Involvement of Akt-mTOR-and hypoxia-induced factor 1-mediated signaling. Autophagy 2011, 7.
154. González Sarrías, A.; Espín, J. C.; Tomás Barberán, F. A.; García Conesa, M. T. Gene expression, cell cycle arrest and MAPK signalling regulation in Caco 2 cells exposed to ellagic acid and its metabolites, urolithins. Mol. Nutr. Food Res. 2009, 53, 686-698.
155. Larrosa, M.; Tomas-Barberan, F. A.; Espin, J. C. The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon
156. Scarlatti, F.; Maffei, R.; Beau, I.; Codogno, P.; Ghidoni, R. Role of non-canonical beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells. Cell Death Differentiation 2008, 15, 1318-1329.