Natural products as promising antitumoral agents in breast cancer: Mechanisms of action and molecular targets

Mini-Reviews in Medicinal Chemistry

Volumn 16, Issue 8, 2016, Pages 596-604

  Bonofiglio, Daniela ^a   Giordano, Cinzia ^a   De Amicis, Francesca ^a   Lanzino, Marilena ^a   Andò, Sebastiano ^a  

^a UNIVERSITY OF CALABRIA   (Italy)

Author keywords

Breast cancer; Epigallocatechin gallate; Oldenlandia diffusa; Omega 3 fatty acids; Resveratrol; Ziziphus jujube

Indexed keywords

ANTINEOPLASTIC AGENT; BETULIC ACID; DOCOSAHEXAENOIC ACID; EPIGALLOCATECHIN GALLATE; GLUTAMATE CYSTEINE LIGASE; HEME OXYGENASE 1; ICOSAPENTAENOIC ACID; MANGANESE SUPEROXIDE DISMUTASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; NATURAL PRODUCT; OLEANOLIC ACID; OMEGA 3 FATTY ACID; PHYTOALEXIN; PROTEIN KINASE B; RESVERATROL; TRANSCRIPTION FACTOR NF E2; URSOLIC ACID; BIOLOGICAL PRODUCT;

APOPTOSIS; ARTICLE; AUTOPHAGY; BREAST CANCER; CARCINOGENESIS; CELL CYCLE; CELL DEATH; CELL GROWTH; DRUG MECHANISM; ENZYME REGULATION; GENE EXPRESSION; HUMAN; MOLECULARLY TARGETED THERAPY; OLDENLANDIA; OXIDATIVE STRESS; ZIZIPHUS; ANIMAL; BREAST NEOPLASMS; CELL PROLIFERATION; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; FEMALE; ISOLATION AND PURIFICATION; MEDICINAL PLANT; METABOLISM; PATHOLOGY;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BIOLOGICAL PRODUCTS; BREAST NEOPLASMS; CELL PROLIFERATION; FEMALE; HUMANS; MOLECULAR STRUCTURE; MOLECULAR TARGETED THERAPY; PLANTS, MEDICINAL;

EID: 84961631719     PISSN: 13895575     EISSN: 18755607     Source Type: Journal    
DOI: 10.2174/1389557515666150709110959     Document Type: Article

References (113)

1. Forouzanfar, M.H.; Foreman, K.J.; Delossantos, A.M.; Lozano, R.; Lopez, A.D.; Murray, C.J.; Naghavi, M. Breast and cervical cancer in 187 countries between 1980 and 2010: a systematic analysis. Lancet, 2011, 378, 1461-1484.
2. Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin., 2011, 61, 69-90.
3. Glade, M.J. Food nutrition, and the prevention of cancer: a global perspective. American Institute for Cancer Research/World Cancer Research Fund, American Institute for Cancer Research, 1997. Nutrition, 1999, 15, 523-526.
4. Hong, W.K.; Sporn, M.B. Recent advances in chemoprevention of cancer. Science, 1997, 278, 1073-1077.
5. Crew, K.D.; Brown, P.; Greenlee, H.; Bevers, T.B.; Arun, B.; Hudis, C.; McArthur, H.L.; Chang, J.; Rimawi, M.; Vornik, L.; Cornelison, T.L.; Wang, A.; Hibshoosh, H.; Ahmed, A.; Terry, M.B.; Santella, R.M.; Lippman, S.M.; Hershman, D.L. Phase IB randomized, double-blinded, placebo-controlled, dose escalation study of polyphenon E in women with hormone receptor-negative breast cancer. Cancer Prev. Res. (Phila), 2012, 5, 1144-1154.
6. Reddy, L.; Odhav, B.; Bhoola, K.D. Natural products for cancer prevention: a global perspective. Pharmacol. Ther., 2003, 99, 1-13.
7. Block, G.; Patterson, B.; Subar, A. Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr. Cancer, 1992, 18, 1-29.
8. Benetou, V.; Orfanos, P.; Lagiou, P.; Trichopoulos, D.; Boffetta, P.; Trichopoulou, A. Vegetables and fruits in relation to cancer risk: evidence from the Greek EPIC cohort study. Cancer Epidemiol. Biomarkers Prev., 2008, 17, 387-392.
9. Freedman, N.D.; Park, Y.; Subar, A.F.; Hollenbeck, A.R.; Leitzmann, M.F.; Schatzkin, A.; Abnet, C.C. Fruit and vegetable intake and head and neck cancer risk in a large United States prospective cohort study. Int. J. Cancer, 2008, 122, 2330-2336.
10. Steinmetz, K.A.; Potter, J.D. Vegetables, fruit, and cancer prevention: a review. J. Am. Diet Assoc., 1996, 96, 1027-1039.
11. Hirayama, T. Epidemiology of prostate cancer with special reference to the role of diet. Natl. Cancer Inst. Monogr., 1979, 149-155.
12. Shekelle, R.B.; Lepper, M.; Liu, S.; Maliza, C.; Raynor, W.J., Jr.; Rossof, A.H.; Paul, O.; Shryock, A.M.; Stamler, J. Dietary vitamin A and risk of cancer in the Western Electric study. Lancet, 1981, 2, 1185-1190.
13. Kvale, G.; Bjelke, E.; Gart, J.J. Dietary habits and lung cancer risk. Int. J. Cancer, 1983, 31, 397-405.
14. Paganini-Hill, A.; Chao, A.; Ross, R.K.; Henderson, B.E.; Vitamin A. beta-carotene, and the risk of cancer: a prospective study. J. Natl. Cancer Inst., 1987, 79, 443-448.
15. Hirayama, T. A large scale cohort study on cancer risks by diet-- with special reference to the risk reducing effects of green-yellow vegetable consumption. Princess Takamatsu Symp., 1985, 16, 41- 53.
16. Colditz, G.A.; Branch, L.G.; Lipnick, R.J.; Willett, W.C.; Rosner, B.; Posner, B.M.; Hennekens, C.H. Increased green and yellow vegetable intake and lowered cancer deaths in an elderly population. Am. J. Clin. Nutr., 1985, 41, 32-36.
17. Wang, L.D.; Hammond, E.C. Lung cancer, fruit, green salad and vitamin pills. Chin. Med. J. (Engl.), 1985, 98, 206-210.
18. Toniolo, P.; Van Kappel, A.L.; Akhmedkhanov, A.; Ferrari, P.; Kato, I.; Shore, R.E.; Riboli, E. Serum carotenoids and breast cancer. Am. J. Epidemiol., 2001, 153, 1142-1147.
19. Dorgan, J.F.; Sowell, A.; Swanson, C.A.; Potischman, N.; Miller, R.; Schussler, N.; Stephenson, H.E., Jr. Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States). Cancer Causes Control, 1998, 9, 89-97.
20. Yiannakopoulou, E. Effect of green tea catechins on breast carcinogenesis: a systematic review of in-vitro and in-vivo experimental studies. Eur. J. Cancer Prev., 2014, 23, 84-89.
21. Bishayee, A.; Ahmed, S.; Brankov, N.; Perloff, M. Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer. Front. Biosci. (Landmark Ed), 2011, 16, 980-996.
22. Signori, C.; El-Bayoumy, K.; Russo, J.; Thompson, H.J.; Richie, J.P.; Hartman, T.J.; Manni, A. Chemoprevention of breast cancer by fish oil in preclinical models: trials and tribulations. Cancer Res., 2011, 71, 6091-6096.
23. Jang, M.; Cai, L.; Udeani, G.O.; Slowing, K.V.; Thomas, C.F.; Beecher, C.W.; Fong, H.H.; Farnsworth, N.R.; Kinghorn, A.D.; Mehta, R.G.; Moon, R.C.; Pezzuto, J.M. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 1997, 275, 218-220.
24. Howells, L.M.; Berry, D.P.; Elliott, P.J.; Jacobson, E.W.; Hoffmann, E.; Hegarty, B.; Brown, K.; Steward, W.P.; Gescher, A.J. Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases--safety, pharmacokinetics, and pharmacodynamics. Cancer Prev. Res. (Phila.), 2011, 4, 1419-1425.
25. Zhu, W.; Qin, W.; Zhang, K.; Rottinghaus, G.E.; Chen, Y.C.; Kliethermes, B.; Sauter, E.R. Trans-resveratrol alters mammary promoter hypermethylation in women at increased risk for breast cancer. Nutr. Cancer, 2012, 64, 393-400.
26. Moiseeva, E.P.; Manson, M.M. dietary chemopreventive phytochemicals: too little or too much? Cancer Prev. Res., 2009, 2, 611-616.
27. Walle, T.; Hsieh, F.; DeLegge, M.H.; Oatis, J.E.; Walle, U.K. High absorption but very low bioavaibility of oral resveratrol in humans. Drug Metab. Dispos., 2004, 32, 1377-1382.
28. Yu, S.S.; Spicer, D.V.; Hawes, D.; Tseng, C.C.; Yang, C.S.; Pike, M.C.; Wu, A.H. Biological effects of green tea capsule supplementation in pre-surgery postmenopausal breast cancer patients. Front. Oncol., 2013, 3, 298.
29. Nakachi, K.; Suemasu, K.; Suga, K.; Takeo, T.; Imai, K.; Higashi, Y. Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn. J. Cancer Res., 1998, 89, 254-261.
30. Inoue, M.; Tajima, K.; Mizutani, M.; Iwata, H.; Iwase, T.; Miura, S.; Hirose, K.; Hamajima, N.; Tominaga, S. Regular consumption of green tea and the risk of breast cancer recurrence: follow-up study from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. Cancer Lett., 2001, 167, 175-182.
31. Zheng, J.S.; Hu, X.J.; Zhao, Y.M.; Yang, J.; Li, D. Intake of fish and marine n-3 polyunsaturated fatty acids and risk of breast cancer: meta-analysis of data from 21 independent prospective cohort studies. Bmj, 2013, 346, f3706.
32. Schley, P.D.; Jijon, H.B.; Robinson, L.E.; Field, C.J. Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells. Breast Cancer Res. Treat., 2005, 92, 187-195.
33. Rovito, D.; Giordano, C.; Vizza, D.; Plastina, P.; Barone, I.; Casaburi, I.; Lanzino, M.; De Amicis, F.; Sisci, D.; Mauro, L.; Aquila, S.; Catalano, S.; Bonofiglio, D.; Andò, S. Omega-3 PUFA ethanolamides DHEA and EPEA induce autophagy through PPARgamma activation in MCF-7 breast cancer cells. J. Cell. Physiol., 2013, 228, 1314-1322.
34. Corsetto, P.A.; Montorfano, G.; Zava, S.; Jovenitti, I.E.; Cremona, A.; Berra, B.; Rizzo, A.M. Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane. Lipids Health Dis., 2011, 10, 73.
35. Kachhap, S.K.; Dange, P.P.; Santani, R.H.; Sawant, S.S.; Ghosh, S.N. Effect of omega-3 fatty acid (docosahexanoic acid) on BRCA1 gene expression and growth in MCF-7 cell line. Cancer Biother. Radiopharm., 2001, 16, 257-263.
36. Harvey, K.A.; Xu, Z.; Whitley, P.; Davisson, V.J.; Siddiqui, R.A. Characterization of anticancer properties of 2,6-diisopropylphenoldocosahexaenoate and analogues in breast cancer cells. Bioorg. Med. Chem., 2010, 18, 1866-1874.
37. Le Corre, L.; Chalabi, N.; Delort, L.; Bignon, Y.J.; Bernard-Gallon, D.J. Resveratrol and breast cancer chemoprevention: molecular mechanisms. Mol. Nutr. Food Res., 2005, 49, 462-471.
38. Gupta, S.C.; Kim, J.H.; Prasad, S.; Aggarwal, B.B. Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer Metastasis Rev., 2010, 29, 405-434.
39. Brakenhielm, E.; Cao, R.; Cao, Y. Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes. Faseb J., 2001, 15, 1798-1800.
40. Lu, R.; Serrero, G. Resveratrol, a natural product derived from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells. J. Cell. Physiol., 1999, 179, 297-304.
41. Nakagawa, H.; Kiyozuka, Y.; Uemura, Y.; Senzaki, H.; Shikata, N.; Hioki, K.; Tsubura, A. Resveratrol inhibits human breast cancer cell growth and may mitigate the effect of linoleic acid, a potent breast cancer cell stimulator. J Cancer Res. Clin. Oncol., 2001, 127, 258-264.
42. Wu, A.H.; Butler, L.M. Green tea and breast cancer. Mol. Nutr. Food Res., 2011, 55, 921-930.
43. De Amicis, F.; Perri, A.; Vizza, D.; Russo, A.; Panno, M.L.; Bonofiglio, D.; Giordano, C.; Mauro, L.; Aquila, S.; Tramontano, D.; Andò, S. Epigallocatechin gallate inhibits growth and epithelial-to-mesenchymal transition in human thyroid carcinoma cell lines. J. Cell. Physiol., 2013, 228, 2054-2062.
44. De Amicis, F.; Russo, A.; Avena, P.; Santoro, M.; Vivacqua, A.; Bonofiglio, D.; Mauro, L.; Aquila, S.; Tramontano, D.; Fuqua, S.A.; Andò, S. In vitro mechanism for downregulation of ER-alpha expression by epigallocatechin gallate in ER+/PR+ human breast cancer cells. Mol. Nutr. Food Res., 2013, 57, 840-853.
45. Liby, K.T.; Yore, M.M.; Sporn, M.B. Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nat. Rev. Cancer, 2007, 7, 357-369.
46. Sun, Y.F.; Song, C.K.; Viernstein, H.; Unger, F.; Liang, Z.S. Apoptosis of human breast cancer cells induced by microencapsulated betulinic acid from sour jujube fruits through the mitochondria transduction pathway. Food Chem., 2013, 138, 1998-2007.
47. Gao, Q.H.; Wu, C.S.; Wang, M. The jujube (Ziziphus jujuba Mill.) fruit: a review of current knowledge of fruit composition and health benefits. J. Agric. Food Chem., 2013, 61, 3351-3363.
48. Goyal, R.; Sharma, P.L.; Singh, M. Possible attenuation of nitric oxide expression in anti-inflammatory effect of Ziziphus jujuba in rat. J. Nat. Med., 2011, 65, 514-518.
49. Gu, G.; Barone, I.; Gelsomino, L.; Giordano, C.; Bonofiglio, D.; Statti, G.; Menichini, F.; Catalano, S.; Andò, S. Oldenlandia diffusa extracts exert antiproliferative and apoptotic effects on human breast cancer cells through ERalpha/Sp1-mediated p53 activation. J. Cell. Physiol., 2012, 227, 3363-3372.
50. Plastina, P.; Bonofiglio, D.; Vizza, D.; Fazio, A.; Rovito, D.; Giordano, C.; Barone, I.; Catalano, S.; Gabriele, B. Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. J. Ethnopharmacol., 2012, 140, 325-332.
51. Gartel, A.L.; Radhakrishnan, S.K. Lost in transcription: p21 repression, mechanisms, and consequences. Cancer Res., 2005, 65, 3980-3985.
52. Chu, I.M.; Hengst, L.; Slingerland, J.M. The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat. Rev. Cancer, 2008, 8, 253-267.
53. May, P.; May, E. Twenty years of p53 research: structural and functional aspects of the p53 protein. Oncogene, 1999, 18, 7621- 7636.
54. Haupt, S.; Berger, M.; Goldberg, Z.; Haupt, Y. Apoptosis - the p53 network. J. Cell. Sci., 2003, 116, 4077-4085.
55. Chamras, H.; Ardashian, A.; Heber, D.; Glaspy, J.A. Fatty acid modulation of MCF-7 human breast cancer cell proliferation, apoptosis and differentiation. J. Nutr. Biochem., 2002, 13, 711-716.
56. Zhang, H.; Zhou, L.; Shi, W.; Song, N.; Yu, K.; Gu, Y. A mechanism underlying the effects of polyunsaturated fatty acids on breast cancer. Int. J. Mol. Med., 2012, 30, 487-494.
57. Serrero, G.; Lu, R. Effect of resveratrol on the expression of autocrine growth modulators in human breast cancer cells. Antioxid. Redox Signal, 2001, 3, 969-979.
58. De Amicis, F.; Giordano, F.; Vivacqua, A.; Pellegrino, M.; Panno, M.L.; Tramontano, D.; Fuqua, S.A.; Andò, S. Resveratrol, through NF-Y/p53/Sin3/HDAC1 complex phosphorylation, inhibits estrogen receptor alpha gene expression via p38MAPK/CK2 signaling in human breast cancer cells. Faseb J., 2011, 25, 3695- 3707.
59. Leon-Galicia, I.; Diaz-Chavez, J.; Garcia-Villa, E.; Uribe-Figueroa, L.; Hidalgo-Miranda, A.; Herrera, L.A.; Alvarez-Rios, E.; Garcia- Mena, J.; Gariglio, P. Resveratrol induces downregulation of DNA repair genes in MCF-7 human breast cancer cells. Eur. J. Cancer Prev., 2013, 22, 11-20.
60. Mgbonyebi, O.P.; Russo, J.; Russo, I.H. Antiproliferative effect of synthetic resveratrol on human breast epithelial cells. Int. J. Oncol., 1998, 12, 865-869.
61. Pozo-Guisado, E.; Alvarez-Barrientos, A.; Mulero-Navarro, S.; Santiago-Josefat, B.; Fernandez-Salguero, P.M. The antiproliferative activity of resveratrol results in apoptosis in MCF- 7 but not in MDA-MB-231 human breast cancer cells: cell-specific alteration of the cell cycle. Biochem. Pharmacol., 2002, 64, 1375- 1386.
62. Braicu, C.; Gherman, C.D.; Irimie, A.; Berindan-Neagoe, I. Epigallocatechin-3-Gallate (EGCG) inhibits cell proliferation and migratory behaviour of triple negative breast cancer cells. J. Nanosci. Nanotechnol., 2013, 13, 632-637.
63. Pianetti, S.; Guo, S.; Kavanagh, K.T.; Sonenshein, G.E. Green tea polyphenol epigallocatechin-3 gallate inhibits Her-2/neu signaling, proliferation, and transformed phenotype of breast cancer cells. Cancer Res., 2002, 62, 652-655.
64. Alshatwi, A.A. Catechin hydrate suppresses MCF-7 proliferation through TP53/Caspase-mediated apoptosis. J Exp Clin. Cancer Res., 2010, 29, 167.
65. Liang, Y.C.; Lin-Shiau, S.Y.; Chen, C.F.; Lin, J.K. Inhibition of cyclin-dependent kinases 2 and 4 activities as well as induction of Cdk inhibitors p21 and p27 during growth arrest of human breast carcinoma cells by (-)-epigallocatechin-3-gallate. J. Cell. Biochem., 1999, 75, 1-12.
66. Masuda, M.; Suzui, M.; Lim, J.T.; Weinstein, I.B. 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., 2003, 9, 3486-3491.
67. Belguise, K.; Guo, S.; Sonenshein, G.E. Activation of FOXO3a by the green tea polyphenol epigallocatechin-3-gallate induces estrogen receptor alpha expression reversing invasive phenotype of breast cancer cells. Cancer Res., 2007, 67, 5763-5770.
68. Farabegoli, F.; Barbi, C.; Lambertini, E.; Piva, R. (-)- Epigallocatechin-3-gallate downregulates estrogen receptor alpha function in MCF-7 breast carcinoma cells. Cancer Detect. Prev., 2007, 31, 499-504.
69. Farabegoli, F.; Papi, A.; Bartolini, G.; Ostan, R.; Orlandi, M. (-)- Epigallocatechin-3-gallate downregulates Pg-P and BCRP in a tamoxifen resistant MCF-7 cell line. Phytomedicine, 2010, 17, 356- 362.
70. Kim, J.; Zhang, X.; Rieger-Christ, K.M.; Summerhayes, I.C.; Wazer, D.E.; Paulson, K.E.; Yee, A.S. Suppression of Wnt signaling by the green tea compound (-)-epigallocatechin 3-gallate (EGCG) in invasive breast cancer cells. Requirement of the transcriptional repressor HBP1. J. Biol. Chem., 2006, 281, 10865- 10875.
71. Karikas, G.A. Anticancer and chemopreventing natural products: some biochemical and therapeutic aspects. J. BUON., 2010, 15, 627-638.
72. Karikas, G.A. Chemoprevention molecular and biochemical mechanisms involved in cancer control and management. Health Science J., 2011, 5, 149-156.
73. Mirza, S.; Sharma, G.; Parshad, R.; Gupta, S.D.; Pandya, P.; Ralhan, R. Expression of DNA Methyltransferases in breast cancer patients and to analyze the effect of natural compounds on DNA Methyltransferases and associated proteins. J. Breast Cancer, 2013, 16, 23-31.
74. Liu, J. Pharmacology of oleanolic acid and ursolic acid. J. Ethnopharmacol., 1995, 49, 57-68.
75. Aggarwal, B.B.; Shishodia, S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem. Pharmacol., 2006, 71, 1397-1421.
76. Kim, H.I.; Quan, F.S.; Kim, J.E.; Lee, N.R.; Kim, H.J.; Jo, S.J.; Lee, C.M.; Jang, D.S.; Inn, K.S. Inhibition of estrogen signaling through depletion of estrogen receptor alpha by ursolic acid and betulinic acid from Prunella vulgaris var. lilacina. Biochem. Biophys. Res. Commun., 2014, 451, 282-287.
77. Mallavadhani, U.V.; Vanga, N.R.; Jeengar, M.K.; Naidu, V.G. Synthesis of novel ring-A fused hybrids of oleanolic acid with capabilities to arrest cell cycle and induce apoptosis in breast cancer cells. Eur. J. Med. Chem., 2014, 74, 398-404.
78. Galluzzi, L.; Aaronson, S.A.; Abrams, J.; Alnemri, E.S.; Andrews, D.W.; Baehrecke, E.H.; Bazan, N.G.; Blagosklonny, M.V.; Blomgren, K.; Borner, C.; Bredesen, D.E.; Brenner, C.; Castedo, M.; Cidlowski, J.A.; Ciechanover, A.; Cohen, G.M.; De Laurenzi, V.; De Maria, R.; Deshmukh, M.; Dynlacht, B.D.; El-Deiry, W.S.; Flavell, R.A.; Fulda, S.; Garrido, C.; Golstein, P.; Gougeon, M.L.; Green, D.R.; Gronemeyer, H.; Hajnoczky, G.; Hardwick, J.M.; Hengartner, M.O.; Ichijo, H.; Jaattela, M.; Kepp, O.; Kimchi, A.; Klionsky, D.J.; Knight, R.A.; Kornbluth, S.; Kumar, S.; Levine, B.; Lipton, S.A.; Lugli, E.; Madeo, F.; Malomi, W.; Marine, J.C.; Martin, S.J.; Medema, J.P.; Mehlen, P.; Melino, G.; Moll, U.M.; Morselli, E.; Nagata, S.; Nicholson, D.W.; Nicotera, P.; Nunez, G.; Oren, M.; Penninger, J.; Pervaiz, S.; Peter, M.E.; Piacentini, M.; Prehn, J.H.; Puthalakath, H.; Rabinovich, G.A.; Rizzuto, R.; Rodrigues, C.M.; Rubinsztein, D.C.; Rudel, T.; Scorrano, L.; Simon, H.U.; Steller, H.; Tschopp, J.; Tsujimoto, Y.; Vandenabeele, P.; Vitale, I.; Vousden, K.H.; Youle, R.J.; Yuan, J.; Zhivotovsky, B.; Kroemer, G. Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes. Cell Death Differ., 2009, 16, 1093-1107.
79. Schley, P.D.; Brindley, D.N.; Field, C.J. (n-3) PUFA alter raft lipid composition and decrease epidermal growth factor receptor levels in lipid rafts of human breast cancer cells. J. Nutr., 2007, 137, 548- 553.
80. Sun, H.; Berquin, I.M.; Owens, R.T.; O'Flaherty, J.T.; Edwards, I.J. Peroxisome proliferator-activated receptor gamma-mediated upregulation of syndecan-1 by n-3 fatty acids promotes apoptosis of human breast cancer cells. Cancer Res., 2008, 68, 2912-2919.
81. 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-kappaB. Int. J. Cancer, 2005, 115, 74-84.
82. Alayev, A.; Berger, S.M.; Kramer, M.Y.; Schwartz, N.S.; Holz, M.K. The combination of rapamycin and resveratrol blocks autophagy and induces apoptosis in breast cancer cells. J. Cell. Biochem., 2015, 116(3), 450-7.
83. Roy, A.M.; Baliga, M.S.; Katiyar, S.K. Epigallocatechin-3-gallate induces apoptosis in estrogen receptor-negative human breast carcinoma cells via modulation in protein expression of p53 and Bax and caspase-3 activation. Mol. Cancer Ther., 2005, 4, 81-90.
84. Farabegoli, F.; Govoni, M.; Ciavarella, C.; Orlandi, M.; Papi, A. A RXR ligand 6-OH-11-O-hydroxyphenanthrene with antitumour properties enhances (-)-epigallocatechin-3-gallate activity in three human breast carcinoma cell lines. Biomed. Res. Int., 2014, 2014, 853-086.
85. Gupta, S.; Zhang, D.; Yi, J.; Shao, J. Anticancer activities of Oldenlandia diffusa. J. Herb Pharmacother., 2004, 4, 21-33.
86. Ovesna, Z.; Vachalkova, A.; Horvathova, K.; Tothova, D. Pentacyclic triterpenoic acids: new chemoprotective compounds. Minireview. Neoplasma, 2004, 51, 327-333.
87. Kassi, E.; Sourlingas, T.G.; Spiliotaki, M.; Papoutsi, Z.; Pratsinis, H.; Aligiannis, N.; Moutsatsou, P. Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells. Cancer Invest., 2009, 27, 723-733.
88. Chakravarti, B.; Maurya, R.; Siddiqui, J.A.; Bid, H.K.; Rajendran, S.M.; Yadav, P.P.; Konwar, R. In vitro anti-breast cancer activity of ethanolic extract of Wrightia tomentosa: role of pro-apoptotic effects of oleanolic acid and urosolic acid. J. Ethnopharmacol., 2012, 142, 72-79.
89. Shan, J.Z.; Xuan, Y.Y.; Ruan, S.Q.; Sun, M. Proliferationinhibiting and apoptosis-inducing effects of ursolic acid and oleanolic acid on multi-drug resistance cancer cells in vitro. Chin. J. Integr. Med., 2011, 17, 607-611.
90. Yang, Z.; Klionsky, D.J. Mammalian autophagy: core molecular machinery and signaling regulation. Curr. Opin. Cell. Biol., 2010, 22, 124-131.
91. Mizushima, N.; Komatsu, M. Autophagy: renovation of cells and tissues. Cell, 2011, 147, 728-741.
92. Choi, A.M.; Ryter, S.W.; Levine, B. Autophagy in human health and disease. N. Engl. J. Med., 2013, 368, 1845-1846.
93. Thumm, M.; Egner, R.; Koch, B.; Schlumpberger, M.; Straub, M.; Veenhuis, M.; Wolf, D.H. Isolation of autophagocytosis mutants of Saccharomyces cerevisiae. FEBS Lett., 1994, 349, 275-280.
94. Mizushima, N.; Sugita, H.; Yoshimori, T.; Ohsumi, Y. A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy. J. Biol. Chem., 1998, 273, 33889-33892.
95. 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 Differ., 2008, 15, 1318-1329.
96. Fu, Y.; Chang, H.; Peng, X.; Bai, Q.; Yi, L.; Zhou, Y.; Zhu, J.; Mi, M. Resveratrol inhibits breast cancer stem-like cells and induces autophagy via suppressing Wnt/beta-catenin signaling pathway. PLoS One, 2014, 9, e102535.
97. Liu, J.; Zheng, L.; Ma, L.; Wang, B.; Zhao, Y.; Wu, N.; Liu, G.; Lin, X. Oleanolic acid inhibits proliferation and invasiveness of Kras-transformed cells via autophagy. J. Nutr. Biochem., 2014, 25(11), 1154-60.
98. Zhao, C.; Yin, S.; Dong, Y.; Guo, X.; Fan, L.; Ye, M.; Hu, H. Autophagy-dependent EIF2AK3 activation compromises ursolic acid-induced apoptosis through upregulation of MCL1 in MCF-7 human breast cancer cells. Autophagy, 2013, 9, 196-207.
99. Klaunig, J.E.; Kamendulis, L.M. The role of oxidative stress in carcinogenesis. Annu. Rev. Pharmacol. Toxicol., 2004, 44, 239- 267.
100. Hybertson, B.M.; Gao, B.; Bose, S.K.; McCord, J.M. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol. Aspects Med., 2011, 32, 234-246.
101. Bauer, G. Targeting extracellular ROS signaling of tumor cells. Anticancer Res., 2014, 34, 1467-1482.
102. Arsova-Sarafinovska, Z.; Eken, A.; Matevska, N.; Erdem, O.; Sayal, A.; Savaser, A.; Banev, S.; Petrovski, D.; Dzikova, S.; Georgiev, V.; Sikole, A.; Ozgok, Y.; Suturkova, L.; Dimovski, A.J.; Aydin, A. Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer. Clin. Biochem., 2009, 42, 1228-1235.
103. De Craemer, D.; Pauwels, M.; Hautekeete, M.; Roels, F. Alterations of hepatocellular peroxisomes in patients with cancer. Catalase cytochemistry and morphometry. Cancer, 1993, 71, 3851- 3858.
104. Elchuri, S.; Oberley, T.D.; Qi, W.; Eisenstein, R.S.; Jackson Roberts, L.; Van Remmen, H.; Epstein, C.J.; Huang, T.T. CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene, 2005, 24, 367-380.
105. Kasapovic, J.; Pejic, S.; Todorovic, A.; Stojiljkovic, V.; Pajovic, S.B. Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages. Cell. Biochem. Funct., 2008, 26, 723-730.
106. Sharma, A.; Tripathi, M.; Satyam, A.; Kumar, L. Study of antioxidant levels in patients with multiple myeloma. Leuk. Lymphoma, 2009, 50, 809-815.
107. Vera-Ramirez, L.; Ramirez-Tortosa, M.C.; Sanchez-Rovira, P.; Ramirez-Tortosa, C.L.; Granados-Principal, S.; Lorente, J.A.; Quiles, J.L. Impact of diet on breast cancer risk: a review of experimental and observational studies. Crit. Rev. Food Sci. Nutr., 2013, 53, 49-75.
108. Zhang, H.; Jiang, L.; Ye, S.; Ye, Y.; Ren, F. Systematic evaluation of antioxidant capacities of the ethanolic extract of different tissues of jujube (Ziziphus jujuba Mill.) from China. Food Chem. Toxicol., 2010, 48, 1461-1465.
109. Na, H.K.; Kim, E.H.; Jung, J.H.; Lee, H.H.; Hyun, J.W.; Surh, Y.J. (-)-Epigallocatechin gallate induces Nrf2-mediated antioxidant enzyme expression via activation of PI3K and ERK in human mammary epithelial cells. Arch. Biochem. Biophys., 2008, 476, 171-177.
110. Ramos-Gomez, M.; Kwak, M.K.; Dolan, P.M.; Itoh, K.; Yamamoto, M.; Talalay, P.; Kensler, T.W. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Proc. Natl. Acad. Sci. U S A, 2001, 98, 3410-3415.
111. Xu, C.; Huang, M.T.; Shen, G.; Yuan, X.; Lin, W.; Khor, T.O.; Conney, A.H.; Kong, A.N. Inhibition of 7,12-dimethylbenz(a) anthracene-induced skin tumorigenesis in C57BL/6 mice by sulforaphane is mediated by nuclear factor E2-related factor 2. Cancer Res., 2006, 66, 8293-8296.
112. Singh, B.; Shoulson, R.; Chatterjee, A.; Ronghe, A.; Bhat, N.K.; Dim, D.C.; Bhat, H.K. Resveratrol inhibits estrogen-induced breast carcinogenesis through induction of NRF2-mediated protective pathways. Carcinogenesis, 2014, 35, 1872-1880.
113. Khan, M.A.; Chen, H.C.; Wan, X.X.; Tania, M.; Xu, A.H.; Chen, F.Z.; Zhang, D.Z. Regulatory effects of resveratrol on antioxidant enzymes: a mechanism of growth inhibition and apoptosis induction in cancer cells. Mol. Cells, 2013, 35, 219-225.