Phytochemicals in diets for breast cancer prevention: The importance of resveratrol and ursolic acid

Food Science and Human Wellness

Volumn 1, Issue 1, 2012, Pages 1-13

  Venugopal, Rahul ^a   Liu, Rui Hai ^a  

^a Department of Obstetrics Gynecology   (United States)

Author keywords

Cancer; Diet and cancer; Phytochemicals; Resveratrol; Ursolic acid

Indexed keywords

EID: 85068965367     PISSN: None     EISSN: 22134530     Source Type: Journal    
DOI: 10.1016/j.fshw.2012.12.001     Document Type: Article

References (147)

1. Ahmedin Jemal, R.S., Cancer statistics, 2010. A Cancer Journal for Clinicians, 2010, 277–300.
2. Temple, N.J., Antioxidants and disease: more questions than answers. Nutrition Research, 2000, 449–459.
3. Willett, W., Diet and health: what should we eat?. Science, 1994, 532–537.
4. Frank, B., Hu, W.C., Optimal diets for prevention of coronary heart disease. The Journal of the American Medical Association, 2002, 2568–2578.
5. Rui Hai Liu, J.H., Potential genotoxicity of chronically elevated nitric oxide: a review. Mutation Research/Reviews in Genetic Toxicology, 1995, 73–89.
6. Ames, B.N., Shigenga, M.K., Hagen, T.M., Oxidants, antioxidants, and the degenerative diseases of aging. Proceedings of the National Academy of Sciences of the United States of America, 1993, 7915–7922.
7. Bruce, N., Ames, L.S., Endogenous mutagens and the causes of aging and cancer. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1991, 3–16.
8. Liu, R.H., Potential synergy of phytochemicals in cancer prevention: mechanism of action. The Journal of Nutrition, 2004, 24795–34855.
9. Lars Ove Dragsted, M.S., Cancer-protective factors in fruits and vegetables: biochemical and biological background. Basic and Clinical Pharmacology and Toxicology, 1993, 116–135.
10. Jie Sun, Y.-F.C., Antioxidant and antiproliferative activities of common fruits. Journal of Agricultural and Food Chemistry, 2002, 7449–7454.
11. Vijayababu, M.R., Kanagaraj, P., Arunkumar, A., Ilangovan, R., Aruldhas, M.M., Arunakaran, J., Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression. Journal of Cancer Research and Clinical Oncology, 2005, 765–771.
12. Fabrice Casagrande, J.-M.D., Effects of structurally related flavonoids on cell cycle progression of human melanoma cells: regulation of cyclin-dependent kinases CDK2 and CDK1. Biochemical Pharmacology, 2001, 1205–1215.
13. Velioglu, Y.S., Mazza, M., Gao, Y.L., Oomah, B.D., Antioxidant activity and total phenolics in selected fruits, vegetables, and grain products. Journal of Agricultural and Food Chemistry, 1998, 4113–4117.
14. Joe, A., Vinson, X.S., Phenol antioxidant quantity and quality in foods: fruits. Journal of Agricultural and Food Chemistry, 2001, 5315–5321.
15. Waladkhani, A.R., Clemens, M.R., Effect of dietary phytochemicals on cancer development (review). International Journal of Molecular Medicine, 1998, 747–753.
16. St Leger, A.S., Cochrane, A.L., Moore, F., Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine. The Lancet, 1979, 1017–1020.
17. Pellegrini, N., Simonetti, P., Brusamolino, A., Bottasso, B., Pareti Fi, Composition of platelet phospholipids after moderate consumption of red wine in healthy volunteers. European Journal of Clinical Nutrition, 1996, 535–544.
18. Renaud, S.a., The French Paradox and Wine Drinking. 1998.
19. Frankel, E.N., German, J.B., Kinsella, J.E., Parks, E., Kanner, J., Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. The Lancet, 1993, 454–457.
20. Takaoka, M., Proceedings of the Imperial Academy: the synthesis of resveratrol and its derivatives. Japan Science and Technology Agency Journal Archives, 16(8), 1940.
21. Pervaiz, S., Resveratrol: The Promise Therein. 2004, Marcel Dekker, New York.
22. Renaud, S.d.L., Wine, alcohol, platelets, and the French paradox for coronary heart disease. The Lancet, 1992, 1523–1526.
23. M. Jang, C.E., Cancer chemopreventive activity of resveratrol, a natural product derived from grapes, Science, 1997, 2118–2220.
24. Catalina Alarcón de la Lastra, I.V., Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications. Molecular Nutrition and Food Research, 2005, 405–430.
25. Nazar Labinskyy, A.C., Vascular dysfunction in aging: potential effects of resveratrol, an anti-inflammatory phytoestrogen. Current Medical Chemistry, 2006, 989–996.
26. Sinclair, J.A., Therapeutic potential of resveratrol: the in vivo evidence. Nature Reviews, 2006, 493–506.
27. Wang, Z., Huang, Y., CAO, K., XU, Y., WU, J.M., Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. International Journal of Molecular Medicine, 2002, 77–79.
28. Kopp, P., Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the ‘French paradox’?. European Journal of Endocrinology, 1998, 619–620.
29. Ferrero, M.E., Bertelli, A.E., Fulgenzi, A., Pellegatta, F., Corsi, M.M., Bonfrate, M., Ferrara, F., De Caterina, R., Giovannini, L., Bertelli, A., Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium. American Journal of Clinical Nutrition, 1998, 1208–1214.
30. Jen-Ying Deng, P.-S.H.-P.-S.-M., Activation of estrogen receptor is crucial for resveratrol-stimulating muscular glucose uptake via both insulin-dependent and -independent pathways. Diabetes, 2008, 1814–1823.
31. Sameer Sharma, M.A., Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats. International Journal of Experimental and Clinical Pharmacology, 2006, 69–75.
32. M. Gentilli, M.J., Resveratrol decreases hyperalgesia induced by carrageenan in the rat hind paw, Life Sciences, 2001, 1317–1321.
33. S.-Y. Shu-Huei Tsai, L.-S.-K., Suppression of nitric oxide synthase and the down-regulation of the activation of NFκB in macrophages by resveratrol, British Journal of Pharmacology, 1999, 673–680.
34. J.J. Docherty, S.T., Resveratrol inhibition of varicella-zoster virus replication in vitro, Antiviral Research (2006) 171–177.
35. D.L. Evers, W.X., 3,4′,5-Trihydroxy-trans-stilbene (resveratrol) inhibits human cytomegalovirus replication and virus-induced cellular signaling, Antiviral Research, 2004, 85–95.
36. Anekonda, T.S., Resveratrol—a boon for treating Alzheimer's disease?. Brain Research Reviews, 2006, 316–326.
37. Kusum Sinha, G.C., Protective effect of resveratrol against oxidative stress in middle cerebral artery occlusion model of stroke in rats. Life Sciences, 2002, 655–665.
38. Jiri Prokop, P.A., Resveratrol and its glycon piceid are stable polyphenols. Journal of Medicinal Food, 2006, 11–14.
39. Rosa, M., Lamuela-Raventos, A.I.-P.-B., Direct HPLC analysis of cis- and trans-resveratrol and piceid isomers in Spanish red vitis vinifera wines. Journal of Agricultural and Food Chemistry, 1995, 281–283.
40. Yu Yana, J.Y., Protection of resveratrol and its analogues against ethanol-induced oxidative DNA damage in human peripheral lymphocytes. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2011, 171–177.
41. X.L. Meng, J.Y., Effects of resveratrol and its derivatives on lipopolysaccharide-induced microglial activation and their structure–activity relationships, Chemico-Biological Interactions, 2008, 51–59.
42. J. Higdon, Resverarol, Linus Pauling Institute: Micronutrient Research for Optimum Health, 2005.
43. W. Jeffrey Hurst, J.A., Survey of the trans-resveratrol and trans-piceid content of cocoa-containing and chocolate products, Journal of Agricultural and Food Chemistry, 2008, 8374–8378.
44. Fulvio Mattivi, F.R., Isolation, characterization, and evolution in red wine vinification of resveratrol monomers. Journal of Agricultural and Food Chemistry, 1995, 1820–1823.
45. Thomas Walle, F.H., High absorption but very low bioavailability of oral resveratrol in humans. Drug Metabolism and Disposition, 2004, 1377–1382.
46. Gilly Regev-Shoshani, O.S., Glycosylation of resveratrol protects it from enzymic oxidation. Biochemical Journal, 2003, 157–163.
47. S.H. Tseng, L.S., Resveratrol suppresses the angiogenesis and tumor growth of gliomas in rats, Clinical Cancer Research, 2004, 2190–2202.
48. L. Fremont, B.L., Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids, Life Science, 1999, 2511–2521.
49. David, J., Boocock, G.E., Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiology, Biomarkers and Prevention, 2007, 1246.
50. Barry, D., Gehm, J.M.-Y., Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proceedings of the National Academy of Sciences of the United States of America, 1997, 14138–14143.
51. J.L. Bowers, T.V., Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta, Endocrinology, 2000, 3657–3667.
52. Ebba Bråkenhielm, R.C., Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes. The Journal of the Federation of American Societies for Experimental Biology, 2001, 1798–1800.
53. Anjana Bhardwaj, G.S.-R.-R., Resveratrol inhibits proliferation, induces apoptosis, and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-κB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells. Journal of the American Society of Hematology, 2007, 2293–2302.
54. Y.A. Kim, C.B., Resveratrol inhibits cell proliferation and induces apoptosis of human breast carcinoma MCF-7 cells, Oncology Reports, 2004, 441–446.
55. Hiroyuki Nakagawa, Y.K., Resveratrol inhibits human breast cancer cell growth and may mitigate the effect of linoleic acid, a potent breast cancer cell stimulator. Journal of Cancer Research and Clinical Oncology, 2001, 258–264.
56. C.A. Rice-Evans, M.N., The relative antioxidant activities of plant-derived polyphenolic flavonoids, Free Radical Research, 1995, 375–383.
57. Athina Damianaki, E.B.-M., Potent inhibitory action of red wine polyphenols. Journal of Cellular Biochemistry, 2000, 429–441.
58. Lu, G.S., Effect of resveratrol on the expression of autocrine growth modulators in human breast cancer cells. Antioxidants and Redox Signaling, 2001, 969–979.
59. O.P. Mgbonyebi, R.J., Antiproliferative effect of synthetic resveratrol on human breast epithelial cells, International Journal of Oncology, 1998, 865–869.
60. Krishna, P.L., Bhat, D.L., Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models. Cancer Research, 2001, 7456–7463.
61. Venkata Mahidhar Yenugonda, Y.K., Trans-resveratrol boronic acid exhibits enhanced anti-proliferative activity on estrogen-dependent MCF-7 breast cancer cells. Cancer Biology and Therapy, 2012, 1–10.
62. R.C. Moon, M.R., Cancer chemoprevention by retinoids: animal models, Methods in Enzymology, 1990, 395–406.
63. Sebastian Günthera, C.R., Polyphenols prevent cell shedding from mouse mammary cancer spheroids and inhibit cancer cell invasion in confrontation cultures derived from embryonic stem cells. Cancer Letters, 2007, 25–35.
64. Mutsuya Sato, R.-J.P., Prepubertal resveratrol exposure accelerates N-methyl-N-nitroso urea-induced mammary carcinoma in female Sprague–Dawley rats. Cancer Letters, 2003, 137–145.
65. M. Emilia Juan, M.P., The daily oral administration of high doses of trans-resveratrol to rats for 28 days is not harmful, The Journal of Nutrition, 2002, 257–260.
66. Stina Garvin, K.Ö., Resveratrol induces apoptosis and inhibits angiogenesis in human breast cancer xenografts in vivo. Cancer Letters, 2006, 113–122.
67. Ebba Bråkenhielm, R.C., Suppression of angiogenesis, tumor growth, and wound healing by resveratrol, a natural compound in red wine and grapes. The FASEB Journal, 2001.
68. Feng-Yao Tang, Y.-C.S.-C.-S.-S., Resveratrol inhibits migration and invasion of human breast-cancer cells. Molecular Nutrition and Food Research, 2008, 683–691.
69. Donglei Zhang, M.B.-E., Dual regulation of MMP-2 expression by the type 1 insulin-like growth factor receptor. Journal of Biological Chemistry, 2004, 19683–19690.
70. Feng-Yao Tang, E.-P.I.-C., Resveratrol inhibits heregulin-β1-mediated matrix metalloproteinase-9 expression and cell invasion in human breast cancer cells. Journal of Nutriotional Biochemistry, 2008, 287–294.
71. Eulalia Pozo-Guisado, J.M.-N.-B.-B., Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a capase-independent mechanism with downregulation of Bcl-2 and NF-KB. International Journal of Cancer, 2005, 74–84.
72. Hung-Yun Lin, L.L.-M.-Y., Integrin αVß3 contains a receptor site for resveratrol. Journal of the Federation of American Societies for Experimental Biology, 2006, 1742–1744.
73. Tze-Chen Hsieh, C.W., Regulation of p53 and cell proliferation by resveratrol and its derivatives in breast cancer cells: an insilico and biochemical approach targeting integrin. International Journal of Cancer, 2011, 2732–2743.
74. Heng-Yuan Tang, A.S.-Y., Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells. Molecular Cancer Therapeutics, 2006, 2034–2042.
75. P.L. Fustier, L.-S.-J., Resveratrol increases BRCA1 and BRCA2 mRNA expression in breast tumor cell lines, British Journal of Cancer, 2003, 168–172.
76. Marek Muriasa, M.M., Metabolism of resveratrol in breast cancer cell lines: impact of sulfotransferase 1A1 expression on cell growth inhibition. Cancer Letters, 2008, 172–182.
77. M. Emília Juan, E.G.-P., Multidrug resistance proteins restrain the intestinal absorption of trans-resveratrol in rats, The Journal of Nutrition, 2010, 489–495.
78. Irene Alfaras, M.P., Involvement of breast cancer resistance protein (BCRP1/ABCG2) in the bioavailability and tissue distribution of trans-resveratrol in Knockout mice. Journal of Agricultural and Food Chemistry, 2010, 4523–4528.
79. Michaela Miksits, K.W., Expression of sulfotransferases and sulfatases in human breast cancer: impact on resveratrol metabolism. Cancer Letters, 2010, 237–245.
80. Chongwoo Yu, Y.G., Human, rat, and mouse metabolism. Pharmaceutical Research, 2002.
81. Teskac, K., Kristl, J., The evidence for solid lipid nanoparticles mediated cell uptake of resveratrol. International Journal of Pharmaceutics, 2010, 61–69.
82. Walter Jager, A.G., Metabolomic analysis of resveratrol-induced effects in the human breast cancer cell lines MCF-7 and MDA-MB-231. Journal of Integrative Biology, 2011.
83. Koen van de Wetering, A.B., Intestinal breast cancer resistance protein (BCRP)/Bcrp1 and multidrug resistance protein 3 (MRP3)/Mrp3 are involved in the pharmacokinetics of resveratrol. Molecular Pharmacology, 2009, 876–885.
84. Kotha Subbaramaiah, W.J., Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. The Journal of Biological Chemistry, 1998, 21875–21882.
85. Young Bin Hong, H.J., Inhibition of cell proliferation by a resveratrol analog in human pancreatic and breast cancer cells. Experimental and Molecular Medicine, 2009, 151–160.
86. F. Scarlatti, R.M., Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells, Cell Death and Differentiation, 2008, 1318–1329.
87. Robert, F., Casper, M.Q.-F., Resveratrol has antagonist activity on the aryl hydrocarbon receptor: implications for prevention of dioxin toxicity. Molecular Pharmacology, 1999, 784–790.
88. Laura MacPherson, J.M., Inhibition of aryl hydrocarbon receptor-dependent transcription by resveratrol or kaempferol is independent of estrogen receptor alpha expression in human breast cancer cells. Cancer Letters, 2010, 119–129.
89. R. Zamora-Ros, A.-L.C.-R., 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, The British Journal of Nutrition, 2007, 188–196.
90. M.V.-d.-S.-L.-F.-d.-S. Luis Almeida, Pharmacokinetic and safety profile of transresveratrol in a rising multiple-dose study in healthy, Molecular Nutrition and Food Research, 2009.
91. C.E.M.K., Petroleum ether- and ether-soluble constituents of cranberry pomace, Journal of Biological Chemistry, 1934, 643–653.
92. Miwako Kondo, S.L., Ursolic acid and its esters: occurrence in cranberries and other Vaccinium fruit and effects on matrix metalloproteinase activity in DU145 prostate tumor cells. Journal of the Science of Food and Agriculture, 2011, 789–796.
93. L. Novotný, V.A., Ursolic acid: an anti-tumorigenic and chemopreventive activity. Minireview, Neoplasma, 2001, 241–246.
94. J.Z. Shan, X.Y., Proliferation-inhibiting and apoptosis-inducing effects of ursolic acid and oleanolic acid on multi-drug resistance cancer cells in vitro, Chinese Journal of Integrative Medicine, 2011, 607–611.
95. Kalani, K., Pharmacophore, Y.D., QSAR, and ADME based semisynthesis and in vitro evaluation of ursolic acid analogs for anticancer activity. Journal of Molecular Modeling, 2012, 3389–3413.
96. X. He, L.R., Triterpenoids isolated from apple peels have potent antiproliferative activity and may be partially responsible for apple's anticancer activity, Journal of Agricultural and Food Chemistry, 2007, 4366–4370.
97. Wang, M., Li, J., Shao, Y., et al. Antioxidative and cytotoxic components of highbush blueberry (Vaccinium corymbosum L.). Phytochemicals and Phytopharmaceuticals, 1999, 271–277.
98. Steven, D., Kunkel, C.J., Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease. PLoS ONE, 2012.
99. Yasutaka Ikeda, A.M., Ursolic acid: an anti- and pro-inflammatory triterpenoid. Molecular Nutrition and Food Research, 2008, 26–42.
100. R.K. Croteau, Biochemistry and molecular biology of plants, 2000, 1250–1268.
101. Chappell, J., Biochemistry and molecular biology of the isoprenoid biosynthetic pathway in plants. Annual Review of Plant Physiology and Plant Molecular Biology, 1995, 521–547.
102. S. Binduja, P.V., Ursolic acid isolated from Eucalyptus tereticornis protects against ethanol toxicity in isolated rat hepatocytes, Phytotherapy Research, 2000, 163–166.
103. Akashi, T.F., Biosynthesis of triterpenoids in cultured cells, and regenerated and wild plant organs taraxacum officinale. Phytochemistry, 1994, 303–308.
104. Heijden, R.T., Regulation and enzymology of pentacyclic triterpenoid phytoalexin biosynthesis in cell suspension cultures of Tabernaemontana divaricata. Phytochemistry, 1989, 2981–2988.
105. Baisted, D.J., Sterol and triterpene synthesis in the developing and germinating pea seed. Biochemical Journal, 1971, 375–383.
106. Trojanowska, M.R., Biosynthesis of avenacins and phytosterols in roots of Avena sativa. Phytochemistry, 2000, 153–164.
107. Liu, J., Pharmacology of oleanolic acid and ursolic acid. Journal of Ethnopharmacology, 1995, 57–68.
108. Rosa, T.S., Frighetto, R.M., Isolation of ursolic acid from apple peels by high speed counter-current chromatography. Food Chemistry, 2008, 767–771.
109. Chappell, J., The genetics and molecular genetics of terpene. Current Opinion in Plant Biology, 2002, 151–157.
110. McGarvey, D.J., Terpenoid metabolism. Plant Cell, 1995, 1015–1026.
111. Manez, S.R., Effect of selected triterpenoids on chronic dermal inflammation. European Journal of Pharmacology, 1997, 103–105.
112. Verma, A.K., Inhibition of skin tumor promotion by retinoic acid and its metabolite 5,6-epoxyretinoic acid. Cancer Research, 1980, 2367–2371.
113. Tokuda, H.O., Inhibitory effects of ursolic and oleanolic acid on skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Cancer Letters, 1986, 279–285.
114. Najid, A.S.-R., Characterization of ursolic acid as a lipoxygenase and cyclooxygenase inhibitor using macrophages, platelets and differentiated HL60 leukemic cells. FEBS Letters, 1992, 213–217.
115. Suh, N.H., Novel triterpenoids suppress inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in mouse macrophages. Cancer Research, 1998, 717–723.
116. G.B. Singh, S.S., Anti-inflammatory activity of oleanolic acid in rats and mice, Journal of Pharmacy and Pharmacology, 1992, 456–458.
117. Safety and Toxicity for Ursolic Acid, (08.10.10) from < http://www.mdidea.com/products/herbextract/ursolicacid/data06.html> (retrieved 27.06.12).
118. Su Jin Koh, J.K.-W., Sensitization of ionizing radiation-induced apoptosis by ursolic acid. Free Radical Research, 2012, 339–345.
119. M.B. Gupta, T.B., Antiinflammatory activity of natural products (I) triterpenoids, European Journal of Pharmacology, 1969, 67–70.
120. K. Takagi, E.P., Anti-inflammatory activities of hederagenin and crude saponin isolated from Sapindus mukorossi Gaertn, Chemical and Pharmacological Bulletin, 1980, 1183–1188.
121. M.T. Huang, C.-T.H.-R., Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid, Cancer Research, 1994, 701–708.
122. Shibata, S., Antitumor-promoting and anti-inflammatory activities of licorice priciples and their modified compounds. Chemical Abstracts, 1994.
123. P.-L. Ya-Ling Hsua, K.-C., Proliferative inhibition, cell-cycle dysregulation, and induction of apoptosis by ursolic acid in human non-small cell lung cancer A549 cells, Life Sciences, 2004, 2303–2316.
124. J.H. Dong-Kyoo Kim, M.-A.-W.-K.-Y.-H.-W., Apoptotic activity of ursolic acid may correlate with the inhibition of initiation of DNA replication, International Journal of Cancer, 2000, 629–636.
125. Bharat, B., Aggarwala, S.S., Molecular targets of dietary agents for prevention and therapy of cancer. Biochemical Pharmacology, 2006, 1397–1421.
126. T.H. Rhew, S.P., Effects of ursolic acid on oncogene expression detected by in situ hybridization in mice, Chemical Abstracts, 1993.
127. Yu, K., Vasilenko, L.L., Hypolipemic properties of triterpenoids. Pharmacology and Toxicology, 1982, 66–70.
128. N.P. Seeram, A.L., 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, Journal of Nutritional Biochemistry, 2005, 360–367.
129. S.U. Mertens-Talcott, J.-S.P., Absorption, metabolism and antioxidant effects of pomegranate (Punica granatum L.) polyphenols after ingestion of a standardized extract in healthy human volunteers, Journal of Agricultural and Food Chemistry, 2006, 8956–8961.
130. Z. Dai, N.V., Pomegranate extract inhibits the proliferation and viability of MMTV-Wnt-1 mouse mammary cancer stem cells in vitro, Oncology Reports, 2010, 1087–1091.
131. Tatjana, P., Stanojkovic, A.K.-R., Cytotoxic and cell cycle effects induced by two herbal extracts on human cervix carcinoma and human breast cancer cell lines. Journal of Medicinal Food, 2010, 291–297.
132. Kyung Hun Kim, H.S.-G., Induction of apoptotic cell death by ursolic acid through mitochondrial death pathway and extrinsic death receptor pathway in MDA-MB-231 cells. Archives of Pharmacal Research, 2011, 1363–1372.
133. W. Zhang, L.Y., Experimental study on MCF-7 cell apoptosis induced by ursolic acid, Journal of Chinese Medicinal Materials, 2005, 297–301.
134. Nelshoppen, K.W., Inhibition of 7,1Zdimethylbenz[a]anthracene(DMBA)-induced mammary tumorigenesis and of in vivo formation of mammary DMBA-DNA adducts by rosemary extract. Cancer Letters, 1991, 169–175.
135. Smith, R.E., Antitumor effects of ursolic acid in a mouse model of postmenopausal breast cancer. Nutrition and Cancer, 2010, 1074–1086.
136. E. Kassi, T.G., Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells, Cancer Investigation, 2009, 723–733.
137. Emad, S., Alnemri, D.J., Human ICE/CED-3 protease nomenclature. Cell, 1996, 171.
138. Cha, H., Park, M., Chung, H., et al. Ursolic acid-induced down-regulation of MMP-9 gene is mediated through the nuclear translocation of glucocorticoid receptor in HT1080 human fibrosarcoma cells. Oncogene, 1998, 771–778.
139. Jonat, C., Rahmsdorf, H., Park, K., et al. Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell, 1990, 1189–1204.
140. Jing-song Wang, T.-n.R., Ursolic acid induces apoptosis by suppressing the expression of FoxM1 in MCF-7 human breast cancer cells. Journal of Medical Oncology, 2012, 10–15.
141. C.-H. Chi-Tai Yeh, W.-C., Ursolic acid, a naturally occurring triterpenoid, suppresses migration and invasion of human breast cancer cells by modulating c-Jun N-terminal kinase, Akt and mammalian target of rapamycin signaling, Molecular Nutrition and Food Research, 2010, 1285–1295.
142. Shishir Shishodia, S.M., Ursolic acid inhibits nuclear factor-κB activation induced by carcinogenic agents through suppression of IκBα kinase and p65 phosphorylation. Journal of Cancer Research, 2003, 4375–4383.
143. Kotha Subbaramaiah, P.M., Ursolic acid inhibits cyclooxygenase-2 transcription in human mammary epithelial cells. Journal of Cancer Research, 2000, 2399–2404.
144. M. Castagna, Y.T., Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters, Journal of Biological Chemistry, 1982, 7847–7851.
145. Judith, S., Sebolt-Leopold, D.T., Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Emerging Microbes and Infections, 1999, 810–816.
146. L. Zhang, F.B., Mechanisms of resistance to TRAIL-induced apoptosis in cancer, Cancer Gene Therapy, 2005, 228–237.
147. Sahdeo Prasad, V.R., Ursolic acid, a pentacyclin triterpene, potentiates TRAIL-induced apoptosis through p53-independent up-regulation of death receptors. The Journal of Biological Chemistry, 2011, 5546–5557.