Breast Cancer

, Volume 25, Issue 5, pp 517–528 | Cite as

Ellagic acid, sulforaphane, and ursolic acid in the prevention and therapy of breast cancer: current evidence and future perspectives

  • Md. Sadikuj JamanEmail author
  • Md. Abu Sayeed
Review Article


Globally, breast cancer is the most common cancer and the second leading cause of cancer-related death among women. Surgery, chemotherapy, hormonal therapy, and radiotherapy are currently available treatment options for breast cancer therapy. However, chemotherapy, hormonal therapy, and radiotherapy are often associated with side effects and multidrug resistance, recurrence, and lack of treatment in metastasis are the major problems in the treatment of breast cancer. Recently, dietary phytochemicals have emerged as advantageous agents for the prevention and therapy of cancer due to their safe nature. Ellagic acid (EA), sulforaphane (SF), and ursolic acid (UA), which are found in widely consumed fruits and vegetables, have been shown to inhibit breast cancer cell proliferation and to induce apoptosis. This review encompasses the role of EA, SF, and UA in the fight against breast cancer. Both in vitro and in vivo effects of these agents are presented.


Breast cancer Ellagic acid Sulforaphane Ursolic acid In vitro In vivo 



Protein kinase B


Apoptotic protease activating factor 1


Apoptosis inducing factor


B-cell lymphoma 2


Bcl-2 associated protein X


Bcl-2 associated agonist of cell death


Cyclin-dependent kinase 4


Cell division cycle 2




Cytochrome P45019/1A1/1A2


DNA (cytosine-5)-methyltransferase 1/3a




Estrogen receptor-α


Epidermal growth factor


Epidermal growth factor receptor


Forkhead box M1


Glutathione S-transferase A1


Histone deacetylases


Human epidermal growth factor receptor 2


Human telomerase reverse transcriptase


Jun N-terminal kinase


Microtubule-associated protein light chain 3


Mammalian target of rapamycin


Matrix metalloproteinase-2


Mitogen-activated protein kinases


NAD(P)H quinone dehydrogenase 1


Phosphatase and tensin homolog


Retinoic acid receptor beta 2


Signal transducer and activator of transcription 3


Thioredoxin reductase 1


Vascular endothelial growth factor-2



Md. Abu Sayeed was recipient of PhD fellowship from Polytechnic University of Marche, Italy. Authors would like to thank Dr Golam Gousul Azam, University of Napoli, Italy for helping to improve the manuscript. Authors would also like to thank Dr Massimo Bracci, Polytechnic University of Marche, Italy for reviewing the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.


  1. 1.
    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics 2012. CA Cancer J Clin. 2015;65:87–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Kim TH, Shin YJ, Won AJ, Lee BM, Choi WS, Jung JH, et al. Resveratrol enhances chemosensitivity of doxorubicin in multidrug-resistant human breast cancer cells via increased cellular influx of doxorubicin. Biochim Biophys Acta. 2014;1840:615–25.CrossRefPubMedGoogle Scholar
  3. 3.
    Siddiqui JA, Singh A, Chagtoo M, Singh N, Godbole MM, Chakravarti B. Phytochemicals for breast cancer therapy: current status and future implications. Curr Cancer Drug Targets. 2015;15:116–35.CrossRefPubMedGoogle Scholar
  4. 4.
    Khan A, Aljarbou AN, Aldebasi YH, Faisal SM, Khan MA. Resveratrol suppresses the proliferation of breast cancer cells by inhibiting fatty acid synthase signaling pathway. Cancer Epidemiol. 2014;38:765–72.CrossRefPubMedGoogle Scholar
  5. 5.
    Wang S, Chen R, Zhong Z, Shi Z, Chen M, Wang Y. Epigallocatechin-3-gallate potentiates the effect of curcumin in inducing growth inhibition and apoptosis of resistant breast cancer cells. Am J Chin Med. 2014;42:1279–200.CrossRefPubMedGoogle Scholar
  6. 6.
    Caruso JA, Campana R, Wei C, Su CH, Hanks AM, Bornman WG, et al. Indole-3-carbinol and its N-alkoxy derivatives preferentially target ERα-positive breast cancer cells. Cell Cycle. 2014;13:2587–599.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Reuben SC, Gopalan A, Petit DM, Bishayee A. Modulation of angiogenesis by dietary phytoconstituents in the prevention and intervention of breast cancer. Mol Nutr Food Res. 2012;56:14–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Kado K, Forsyth A, Patel PR, Schwartz JA. Dietary supplements and natural products in breast cancer trials. Front Biosci. 2012;4:546–67.CrossRefGoogle Scholar
  9. 9.
    Yarla NS, Bishayee A, Sethi G, Reddanna P, Kalle AM, Dhananjaya BL, et al. Targeting arachidonic acid pathway by natural products for cancer prevention and therapy. Semin Cancer Biol. 2016;40:48–81.CrossRefPubMedGoogle Scholar
  10. 10.
    Yang L, Palliyaguru DL, Kensler TW. Frugal chemoprevention: targeting Nrf2 with foods rich in sulforaphane. Semin Oncol. 2016;43:146–53.CrossRefPubMedGoogle Scholar
  11. 11.
    Yager L, Hellmold N, Joo HA, Putnam MT, Rossi E, Stafford C, et al. New structural patterns in moribund grammar: case marking in heritage German. Front Psychol. 2015;20:1716.Google Scholar
  12. 12.
    Aiyer HS, Warri AM, Woode DR, Hilakivi-Clarke L, Clarke R. Influence of berry polyphenols on receptor signaling and cell-death pathways: implications for breast cancer prevention. J Agric Food Chem. 2012;60:5693–708.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Nuñez-Sánchez MA, García-Villalba R, Monedero-Saiz T, García-Talavera NV, Gómez-Sánchez MB, Sánchez-Álvarez C, et al. Targeted metabolomics profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients. Mol Nutr Food Res. 2014;58:1199–211.CrossRefPubMedGoogle Scholar
  14. 14.
    Espín JC, Larrosa M, García-Conesa MT, Tomás-Barberán F. Biological significance of urolithins, the gut microbial ellagic Acid-derived metabolites: the evidence so far. Evid Based Complement Alternat Med. 2013;2013:270418.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Landete JM. Ellagitannins, ellagic acid and their derived metabolites: a review about source, metabolism, functions and health. Food Res Int. 2011;44:1150–160.CrossRefGoogle Scholar
  16. 16.
    Seeram NP, 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;348:63–8.CrossRefPubMedGoogle Scholar
  17. 17.
    González-Barrio R, Borges G, Mullen W, Crozier A. Bioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy humans and subjects with an ileostomy. J Agric Food Chem. 2010;58:3933–939.CrossRefPubMedGoogle Scholar
  18. 18.
    Zhang Y. The molecular basis that unifies the metabolism, cellular uptake and chemopreventive activities of dietary isothiocyanates. Carcinogenesis. 2012;33:2–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Egner PA, Kensler TW, Chen JG, Gange SJ, Groopman JD, Friesen MD. Quantification of sulforaphane mercapturic acid pathway conjugates in human urine by high-performance liquid chromatography and isotope-dilution tandem mass spectrometry. Chem Res Toxicol. 2008;21:1991–996.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gasper AV, Al-Janobi A, Smith JA, Bacon JR, Fortun P, Atherton C, et al. Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli. Am J Clin Nutr. 2005;82:1283–291.CrossRefPubMedGoogle Scholar
  21. 21.
    Veeranki OL, Bhattacharya A, Marshall JR, Zhang Y. Organ-specific exposure and response to sulforaphane, a key chemopreventive ingredient in broccoli: implications for cancer prevention. Br J Nutr. 2013;109:25–2.CrossRefPubMedGoogle Scholar
  22. 22.
    Clarke JD, Hsu A, Williams DE, Dashwood RH, Stevens JF, Yamamoto M, et al. Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice. Pharm Res. 2011;28:3171–179.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Cornblatt BS, Ye L, Dinkova-Kostova AT, Erb M, Fahey JW, Singh NK, et al. Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis. 2007;28:1485–490.CrossRefPubMedGoogle Scholar
  24. 24.
    Chen H, Gao Y, Wang A, Zhou X, Zheng Y, Zhou J. Evolution in medicinal chemistry of ursolic acid derivatives as anticancer agents. Eur J Med Chem. 2015;92:648–55.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Liao Q, Yang W, Jia Y, Chen X, Gao Q, Bi K. LC-MS determination and pharmacokinetic studies of ursolic acid in rat plasma after administration of the traditional chinese medicinal preparation Lu-Ying extract. Yakugaku Zasshi. 2005;125:509–15.CrossRefPubMedGoogle Scholar
  26. 26.
    Xia Y, Wei G, Si D, Liu C. Quantitation of ursolic acid in human plasma by ultra performance liquid chromatography tandem mass spectrometry and its pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2011;879:219–24.CrossRefPubMedGoogle Scholar
  27. 27.
    Shi L, Gao X, Li X, Jiang N, Luo F, Gu C, et al. Ellagic acid enhances the efficacy of PI3K Inhibitor GDC-0941 in breast cancer cells. Curr Mol Med. 2015;15:478–86.CrossRefPubMedGoogle Scholar
  28. 28.
    Chen HS, Bai MH, Zhang T, Li GD, Liu M. Ellagic acid induces cell cycle arrest and apoptosis through TGF-β/Smad3 signaling pathway in human breast cancer MCF-7 cells. Int J Oncol. 2015b;46:1730–738.CrossRefPubMedGoogle Scholar
  29. 29.
    Zhang T, Chen HS, Wang LF, Bai MH, Wang YC, Jiang XF, et al. Ellagic acid exerts anti-proliferation effects via modulation of Tgf-β/Smad3 signaling in MCF-7 breast cancer cells. Asian Pac J Cancer Prev. 2014;15:273–76.CrossRefPubMedGoogle Scholar
  30. 30.
    Khan MK, Ansari IA, Khan MS. Dietary phytochemicals as potent chemotherapeutic agents against breast cancer: inhibition of NF-κB pathway via molecular interactions in rel homology domain of its precursor protein p105. Pharmacogn Mag. 2013;9:51–7.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Paluszczak J, Krajka-Kuźniak V, Baer-Dubowska W. The effect of dietary polyphenols on the epigenetic regulation of gene expression in MCF7 breast cancer cells. Toxicol Lett. 2010;192:119–25.CrossRefPubMedGoogle Scholar
  32. 32.
    Strati A, Papoutsi Z, Lianidou E, Moutsatsou P. Effect of ellagic acid on the expression of human telomerase reverse transcriptase (hTERT) alpha + beta + transcript in estrogen receptor-positive MCF-7 breast cancer cells. Clin Biochem. 2009;42:13–4.CrossRefGoogle Scholar
  33. 33.
    Papoutsi Z, Kassi E, Tsiapara A, Fokialakis N, Chrousos GP, Moutsatsou P. Evaluation of estrogenic/antiestrogenic activity of ellagic acid via the estrogen receptor subtypes ERalpha and Erbeta. J Agric Food Chem. 2005;53:7715–720.CrossRefPubMedGoogle Scholar
  34. 34.
    Losso JN, Bansode RR, Trappey A, Bawadi HA, Truax R. In vitro anti-proliferative activities of ellagic acid. J Nutr Biochem. 2004;15:672–78.CrossRefPubMedGoogle Scholar
  35. 35.
    Rocha A, Wang L, Penichet M, Martins-Green M. Pomegranate juice and specific components inhibit cell and molecular processes critical for metastasis of breast cancer. Breast Cancer Res Treat. 2012;136:647–58.CrossRefPubMedGoogle Scholar
  36. 36.
    Shirode AB, Bharali DJ, Nallanthighal S, Coon JK, Mousa SA, Reliene R. Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention. Int J Nanomedicine. 2015;10:475–84.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Munagala R, Aqil F, Vadhanam MV, Gupta RC. MicroRNA ‘signature’ during estrogen-mediated mammary carcinogenesis and its reversal by ellagic acid intervention. Cancer Lett. 2013;339:175–84.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Wang N, Wang ZY, Mo SL, Loo TY, Wang DM, Luo HB, et al. Ellagic acid, a phenolic compound, exerts anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer. Breast Cancer Res Treat. 2012;134:943–55.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Ravoori S, Vadhanam MV, Aqil F, Gupta RC. Inhibition of estrogen-mediated mammary tumorigenesis by blueberry and black raspberry. J Agric Food Chem 2012;60:5547–555.CrossRefGoogle Scholar
  40. 40.
    Vadhanam MV, Ravoori S, Aqil F, Gupta RC. Chemoprevention of mammary carcinogenesis by sustained systemic delivery of ellagic acid. Eur J Cancer Prev. 2011;20:484–91.CrossRefPubMedGoogle Scholar
  41. 41.
    Aiyer HS, Gupta RC. Berries and ellagic acid prevent estrogen-induced mammary tumorigenesis by modulating enzymes of estrogen metabolism. Cancer Prev Res (Phila. 2010;3:727–37.CrossRefGoogle Scholar
  42. 42.
    Aiyer HS, Srinivasan C, Gupta RC. Dietary berries and ellagic acid diminish estrogen-mediated mammary tumorigenesis in ACI rats. Nutr Cancer. 2008;60:227–34.CrossRefPubMedGoogle Scholar
  43. 43.
    Lubecka-Pietruszewska K, Kaufman-Szymczyk A, Stefanska B, Cebula-Obrzut B, Smolewski P, Fabianowska-Majewska K. Sulforaphane alone and in combination with clofarabine epigenetically regulates the expression of DNA methylation-silenced tumour suppressor genes in human breast cancer cells. J Nutrigenet Nutrigenomics. 2015;8:91–101.CrossRefPubMedGoogle Scholar
  44. 44.
    Roy M, Sarkar R, Mukherjee S, Mukherjee A, Biswas J. Sulforaphane inhibits metastatic events in breast cancer cells through genetic and epigenetic regulation. J Carcinog Mutagen. 2015;6:1–8.Google Scholar
  45. 45.
    Licznerska B, Szaefer H, Matuszak I, Murias M, Baer-Dubowska W. Modulating potential of L-sulforaphane in the expression of cytochrome p450 to identify potential targets for breast cancer chemoprevention and therapy using breast cell lines. Phytother Res. 2015;29:93–9.CrossRefPubMedGoogle Scholar
  46. 46.
    Hussain A, Mohsin J, Prabhu SA, Begum S, Nusri Q-A, Harish G, et al. Sulforaphane inhibits growth of human breast cancer cells and augments the therapeutic index of the chemotherapeutic drug, gemcitabine. Asian Pac J Cancer Prev. 2013;14:5855–860.CrossRefPubMedGoogle Scholar
  47. 47.
    Li Q, Yao Y, Eades G, Liu Z, Zhang Y, Zhou Q. Down regulation of miR-140 promotes cancer stem cell formation in basal-like early stage breast cancer. Oncogene 2014;33:2589–600.Google Scholar
  48. 48.
    Lee YR, Noh EM, Han JH, Kim JM, Hwang BM, Kim BS, et al. Sulforaphane controls TPA-induced MMP-9 expression through the NF-κB signaling pathway, but not AP-1, in MCF-7 breast cancer cells. BMB Rep. 2013;46:201–06.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Pawlik A, Wiczk A, Kaczyńska A, Antosiewicz J, Herman-Antosiewicz A. Sulforaphane inhibits growth of phenotypically different breast cancer cells. Eur J Nutr. 2013;52:1949–958.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Sarkar R, Mukherjee S, Biswas J, Roy M. Sulphoraphane, a naturally occurring isothiocyanate induces apoptosis in breast cancer cells by targeting heat shock proteins. Biochem Biophys Res Commun. 2012;427:80–5.CrossRefPubMedGoogle Scholar
  51. 51.
    Sakao K, Singh SV. D,L-sulforaphane-induced apoptosis in human breast cancer cells is regulated by the adapter protein p66Shc. J Cell Biochem. 2012;113:599–10.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Kanematsu S, Uehara N, Miki H, Yoshizawa K, Kawanaka A, Yuri T, et al. Autophagy inhibition enhances sulforaphane-induced apoptosis in human breast cancer cells. Anticancer Res. 2010;30:3381–390.PubMedGoogle Scholar
  53. 53.
    Meeran SM, Patel SN, Tollefsbol TO. Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cell lines. PLoS One. 2010;5:e11457.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Li Y, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, et al. Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res. 2010;16:2580–590.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Azarenko O, Okouneva T, Singletary KW, Jordan MA, Wilson L. Suppression of microtubule dynamic instability and turnover in MCF7 breast cancer cells by sulforaphane. Carcinogenesis. 2008;29:2360–368.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Ramirez MC, Singletary K. Regulation of estrogen receptor alpha expression in human breast cancer cells by sulforaphane. J Nutr Biochem. 2009;20:195–01.CrossRefPubMedGoogle Scholar
  57. 57.
    Jo EH, Kim SH, Ahn NS, Park JS, Hwang JW, Lee YS, et al. Efficacy of sulforaphane is mediated by p38 MAP kinase and caspase-7 activations in ER-positive and COX-2-expressed human breast cancer cells. Eur J Cancer Prev. 2007;16:505–10.CrossRefPubMedGoogle Scholar
  58. 58.
    Pledgie-Tracy A, Sobolewski MD, Davidson NE. Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines. Mol Cancer Ther. 2007;6:1013–021.CrossRefPubMedGoogle Scholar
  59. 59.
    Wang W, Wang S, Howie AF, Beckett GJ, Mithen R, Bao Y. Sulforaphane, erucin, and iberin up-regulate thioredoxin reductase 1 expression in human MCF-7 cells. J Agric Food Chem. 2005;53:1417–421.CrossRefPubMedGoogle Scholar
  60. 60.
    Jackson SJ, Singletary KW. Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. J Nutr. 2004;134:2229–236.CrossRefPubMedGoogle Scholar
  61. 61.
    Sinha S, Shukla S, Khan S, Tollefsbol TO, Meeran SM. Epigenetic reactivation of p21CIP1/WAF1 and KLOTHO by a combination of bioactive dietary supplements is partially ERα-dependent in ERα-negative human breast cancer cells. Mol Cell Endocrinol. 2015;406:102–14.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Kaczyńska A, Świerczyńska J, Herman-Antosiewicz A. Sensitization of HER2 positive Breast Cancer Cells to lapatinib using plants-derived isothiocyanates. Nutr Cancer. 2015;67:976–86.CrossRefPubMedGoogle Scholar
  63. 63.
    Ni M, Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, et al. Targeting androgen receptor in estrogen receptor-negative breast cancer. Cancer Cell. 2011;20:119–31.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Meeran SM, Patel SN, Li Y, Shukla S, Tollefsbol TO. Bioactive dietary supplements reactivate ER expression in ER-negative breast cancer cells by active chromatin modifications. PLoS One. 2012;7:e37748.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Hutzen B, Willis W, Jones S, Cen L, Deangelis S, Fuh B, et al. Dietary agent, benzyl isothiocyanate inhibits signal transducer and activator of transcription 3 phosphorylation and collaborates with sulforaphane in the growth suppression of PANC-1 cancer cells. Cancer Cell Int. 2009;9:24.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Kanematsu S, Yoshizawa K, Uehara N, Miki H, Sasaki T, Kuro M, et al. Sulforaphane inhibits the growth of KPL-1 human breast cancer cells in vitro and suppresses the growth and metastasis of orthotopically transplanted KPL-1 cells in female athymic mice. Oncol Rep. 2011;26:603–08.PubMedGoogle Scholar
  67. 67.
    Jackson SJ, Singletary KW. Sulforaphane: a naturally occurring mammary carcinoma mitotic inhibitor, which disrupts tubulin polymerization. Carcinogenesis. 2004;25:219–27.CrossRefPubMedGoogle Scholar
  68. 68.
    Zhang Y, Kensler TW, Cho CG, Posner GH, Talalay P. Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc Natl Acad Sci USA. 1994;91:3147–150.CrossRefPubMedGoogle Scholar
  69. 69.
    Bishayee A, Ahmed S, Brankov N, Perloff M. Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer. Front Biosci. 2011;16:980–96.CrossRefPubMedCentralGoogle Scholar
  70. 70.
    Sathya S, Sudhagar S, Sarathkumar B, Lakshmi BS. EGFR inhibition by pentacyclic triterpenes exhibit cell cycle and growth arrest in breast cancer cells. Life Sci. 2014;95:53–2.CrossRefPubMedGoogle Scholar
  71. 71.
    Kim HI, Quan FS, Kim JE, Lee NR, Kim HJ, Jo SJ, et al. Inhibition of estrogen signaling through h depletion of estrogen receptor alpha by ursolic acid and betulinic acid from Prunella vulgaris var. lilacina. Biochem Biophys Res Commun 2014;451:282–87.Google Scholar
  72. 72.
    Zhao C, Yin S, Dong Y, Guo X, Fan L, Ye M, et al. Autophagy-dependent EIF2AK3 activation compromises ursolic acid-induced apoptosis through upregulation of MCL1 in MCF-7 human breast cancer cells. Autophagy. 2013;9:196–07.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Wang JS, Ren TN, Xi T. Ursolic acid induces apoptosis by suppressing the expression of FoxM1 in MCF-7 human breast cancer cells. Med Oncol. 2012;29:10–5.CrossRefPubMedGoogle Scholar
  74. 74.
    Kim KH, Seo HS, Choi HS, Choi I, Shin YC, Ko SG. Induction of apoptotic cell death by ursolic acid through mitochondrial death pathway and extrinsic death receptor pathway in MDA-MB-231 cells. Arch Pharm Res. 2011;34:1363–372.CrossRefPubMedGoogle Scholar
  75. 75.
    Yeh CT, Wu CH, Yen GC. 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. Mol Nutr Food Res. 2010;54:1285–295.CrossRefPubMedGoogle Scholar
  76. 76.
    Kassi E, Sourlingas TG, Spiliotaki M, Papoutsi Z, Pratsinis H, Aligiannis N, et al. Ursolic acid triggers apoptosis and Bcl-2 downregulation in MCF-7 breast cancer cells. Cancer Invest. 2009;27:723–33.CrossRefPubMedGoogle Scholar
  77. 77.
    Dar BA, Lone AM, Shah WA, Qurishi MA. Synthesis and screening of ursolic acid-benzylidine derivatives as potential anti-cancer agents. Eur J Med Chem. 2016;23:26 – 2.CrossRefGoogle Scholar
  78. 78.
    Rashid S, Dar BA, Majeed R, Hamid A, Bhat BA. Synthesis and biological evaluation of ursolic acid-triazolyl derivatives as potential anti-cancer agents. Eur J Med Chem 2013;66:238–45.CrossRefGoogle Scholar
  79. 79.
    Liu MC, Yang SJ, Jin LH, Hu DY, Xue W, Song BA, et al. Synthesis and cytotoxicity of novel ursolic acid derivatives containing an acyl piperazine moiety. Eur J Med Chem. 2012;58:128–35.CrossRefPubMedGoogle Scholar
  80. 80.
    Gu G, Barone I, Gelsomino L, Giordano C, Bonofiglio D, Statti G, et al. Oldenlandia diffusa extracts exert antiproliferative and apoptotic effects on human breast cancer cells through ERα/Sp1-mediated p53 activation. J Cell Physiol. 2012;227:3363–372.CrossRefPubMedGoogle Scholar
  81. 81.
    Chakravarti B, Maurya R, Siddiqui JA, Bid HK, Rajendran SM, Yadav PP, et al. 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;142:72–9.CrossRefPubMedGoogle Scholar
  82. 82.
    De Angel RE, Smith SM, Glickman RD, Perkins SN, Hursting SD. Antitumor effects of ursolic acid in a mouse model of postmenopausal breast cancer. Nutr Cancer.2010;62:1074–086.CrossRefPubMedGoogle Scholar
  83. 83.
    Singletary K, MacDonald C, Wallig M. Inhibition by rosemary and carnosol of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumorigenesis and in vivo DMBA-DNA adduct formation. Cancer Lett. 1996;104:43–8.CrossRefPubMedGoogle Scholar
  84. 84.
    Johnson JJ, Nihal M, Siddiqui JA, Scarlett CO, Barley HH, Mukhtar H, et al. Enhancing the bioavailability of resveratrol by combining it with piperine. Mol Nutr Food Res. 2011;55:1169–176.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Hwang JT, Lee YK, Shin JI, Park OJ. Anti-inflammatory and anticarcinogenic effect of genistein alone or in combination with capsaicin in TPA-treated rat mammary glands or mammary cancer cell line. Ann N Y Acad Sci. 2009;1171:415–20.CrossRefPubMedGoogle Scholar
  86. 86.
    Bråkenhielm 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;15:1798–800.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2018

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyUniversity of RajshahiRajshahiBangladesh
  2. 2.Department of Clinical and Molecular SciencesPolytechnic University of MarcheAnconaItaly

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