Archives of Gynecology and Obstetrics

, Volume 285, Issue 4, pp 1145–1151 | Cite as

Antiproliferative activity of lignans against the breast carcinoma cell lines MCF 7 and BT 20

  • Sibylle AbarzuaEmail author
  • Tatsuo Serikawa
  • Marlen Szewczyk
  • Dagmar-Ulrike Richter
  • Birgit Piechulla
  • Volker Briese
Gynecologic Oncology



Phytoestrogens are plant-derived, non-steroidal phytochemicals with anticarcinogenic potential. The major structural classes are the isoflavones and lignans. The aim of this study was to compare the effect of the plant-derived lignans secoisolariciresinol and matairesinol with the human lignans enterodiol and enterolactone as well as with 17β estradiol and tamoxifen on cell proliferation of breast carcinoma cell lines.


The influence of the lignans, 17β estradiol and tamoxifen on cell proliferation was determined using the BrdU test in MCF 7 and BT 20 cell lines.


Enterodiol and enterolactone induced a stronger inhibition of cell growth in MCF 7 and BT 20 cells than secoisolariciresinol and matairesinol. The inhibition effects were less expressed in the BT 20 than in the MCF 7 cells.


The human lignans enterodiol and enterolactone are more biologically active than their precursors secoisolariciresinol and matairesinol, and may be defined as the real drugs in cancer prevention.


Lignans Cell proliferation MCF 7 BT 20 



The authors thank Mrs. C. Bauer and Mrs. E. Greschkowitz for technical assistance.

Conflict of interest



  1. 1.
    Rickard-Bon SE, Thompson LU (2003) The role of flaxseed lignans in hormone-dependent and independent cancer. In: Westcott ND, Muir AD (eds) Flax, the Genus Linum. Taylor and Francis Inc, London, pp 181–203Google Scholar
  2. 2.
    Kulling EK, Watzl W (2003) Phytoöstrogene. Ernährungs-Umschau 50:234–239Google Scholar
  3. 3.
    Lee KH, Xiao Z (2003) Lignans in treatment of cancer and other diseases. Phytochem Rev 2:341–362CrossRefGoogle Scholar
  4. 4.
    Setchell KD (1998) Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr 68:1333S–1346SPubMedGoogle Scholar
  5. 5.
    Plessow D, Waldschläger J, Richter D-U, Jeschke U, Bruer G, Briese V, Friese K (2003) Effects of phytoestrogens on the trophoblast tumour cell lines BeWo and Jeg3. Anticancer Res 23:1081–1086PubMedGoogle Scholar
  6. 6.
    Westcott ND, Muir AD (2003) Chemical studies on the constituents of Linum spp. In: Westcott ND, Muir AD (eds) Flax, the Genus Linum. Taylor and Francis Inc, London, pp 55–73Google Scholar
  7. 7.
    Adlercreutz H (1995) Phytoestrogens: epidemiology and a possible role in cancer protection. Environ Health Perspect 103:103–112PubMedGoogle Scholar
  8. 8.
    Fournier DB, Erdmann JW Jr, Gordon GB (1998) Soy, its components, and cancer prevention: a review of the in vitro, animal, and human data. Cancer Epidemiol Biomarkers Prev 7:1055–1065PubMedGoogle Scholar
  9. 9.
    Zhou JR, Gugger ET, Tanaka T, Guo Y, Blackburn GL, Clinton SK (1999) Soybean phytochemicals inhibit the growth of transplantable human prostata carcinoma and tumor angiogenesis in mice. J Nutr 129:1628–1635PubMedGoogle Scholar
  10. 10.
    Saarinen NM, Power K, Chen J, Thompson LU (2006) Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF-7 human breast cancer xenografts. Int J Cancer 119:925–931PubMedCrossRefGoogle Scholar
  11. 11.
    Waldschläger J, Bergemann C, Ruth W, Effmert U, Jeschke U, Richter D-U, Kragl U, Piechulla B, Briese V (2005) Flax-seed extracts with phytoestrogenic effects on a hormone receptor-positive tumour cell line. Anticancer Res 25:1817–1822PubMedGoogle Scholar
  12. 12.
    Abarzua S, Szewczyk M, Gailus S, Richter D-U, Ruth W, Briese V, Piechulla B (2007) Effects of phytoestrogen extracts from Linum usitatissimum on the Jeg3 human trophoblast tumour cell line. Anticancer Res 27:2053–2058PubMedGoogle Scholar
  13. 13.
    Szewczyk M, Abarzua S, Schlichting A, Richter D-U, Nebe B, Piechulla B, Briese V (2011) Effects of flax extracts from Linum usitatissimum on cell vitality, proliferation and cytotoxicity in human carcinoma breast cell lines in vitro. Eur J Cancer Prev (submitted)Google Scholar
  14. 14.
    Kinghorn AD, Su BN, Jang DS, Chang LC, Lee D, Gu JQ, Carcache-Blanco EJ, Powlus AD, Lee SK, Park EJ, Cuendet M, Gills JJ, Bhat K, Park HS, Mata-Greenwood E, Song LL, Jong MH, Pezzuto JM (2004) Natural inhibitors of carcinogenesis. Planta Med 70:691–705PubMedCrossRefGoogle Scholar
  15. 15.
    Paschke D, Abarzua S, Schlichting A, Richter D-U, Leinweber P, Briese V (2009) Inhibitory effects of bark extracts from Ulmus laevis on endometrial carcinoma: an in vitro study. Eur J Cancer Prev 18:162–168PubMedCrossRefGoogle Scholar
  16. 16.
    Atkinson C, Frankenfeld CL, Lampe JW (2005) Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health. Exp Biol Med 230:155–170Google Scholar
  17. 17.
    Arroo RRJ, Androutsopoulos V, Patel A, Surichan S, Wilsher N, Potter GA (2008) Phytoestrogens as natural prodrugs in cancer prevention: a novel concept. Phytochem Rev 7:431–443CrossRefGoogle Scholar
  18. 18.
    Begum AN, Nicolle C, Mila I, Lapierre C, Nagano K, Fukushima K, Heinonen SM, Adlercreutz H, Remesy C, Scalbert A (2004) Dietary lignins are precursors of mammalian lignans in rats. J Nutr 134:120–127PubMedGoogle Scholar
  19. 19.
    Wang LQ (2002) Mammalian phytoestrogens: enterodiol and enterolactone. J Chromatogr B Analyt Technol Biomed Life Sci 25;777(1–2):289–309Google Scholar
  20. 20.
    Saarinen NM, Wärri A, Airio M, Smeds A, Mäkelä S (2007) Role of dietary lignans in the reduction of breast cancer risk. Mol Nutr Food Res 51(7):857–866PubMedCrossRefGoogle Scholar
  21. 21.
    Mousavi Y, Adlercreutz H (1992) Enterolactone and estradiol inhibit each other’s proliferative effect on MCF-7 breast cancer cells in culture. J Steroid Biochem Mol Biol 41:615–619PubMedCrossRefGoogle Scholar
  22. 22.
    Kinghorn AD, Su BN, Lee D, Gu JQ, Pezzuto JM (2003) Cancer chemopreventive agents discovered by activity-guided fractionation: An update. Curr Org Chem 7:213–226CrossRefGoogle Scholar
  23. 23.
    Wang C, Kurzer MS (1997) Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells. Nutr Cancer 28:236–247PubMedCrossRefGoogle Scholar
  24. 24.
    Adlercreutz H, Mazur W (1997) Phytoestrogens and western diseases. Ann Med 29:95PubMedGoogle Scholar
  25. 25.
    Usui T (2006) Pharmaceutical prospects of phytoestrogens. Endocr J 53:1579–1585CrossRefGoogle Scholar
  26. 26.
    Welshons WV, Murphy CS, Koch R, Galaf G, Jordan VC (1987) Stimulation of breast cancer cells in vitro by the environmental estrogen enterolactone and the phytoestrogen equol. Breast Cancer Res Treat 10:169–175PubMedCrossRefGoogle Scholar
  27. 27.
    Sathyamoorthy N, Wang TT, Phang JM (1994) Stimulation of pS2 expression by diet-derived compounds. Cancer Res 54:957–961PubMedGoogle Scholar
  28. 28.
    Cauley JA, Lucas FL, Kuller LH, Stone K, Browner W, Cummings SR, Study of Osteoporotic Fractures Research Group (1999) Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer. Ann Intern Med 130:270–277PubMedGoogle Scholar
  29. 29.
    Zheng A, Kallio A, Härkönen P (2007) Tamoxifen-induced rapid death of MCF-7 breast cancer cells is mediated via extracellularly signal-regulated kinase signaling and can be abrogated by estrogen. Endocrin 148(6):2764–2777CrossRefGoogle Scholar
  30. 30.
    Todorova VK, Kaufmann Y, Luo S, Klimberg VS (2011) Tamoxifen and raloxifene suppress the proliferation of estrogen receptor-negative cells through inhibition of glutamine uptake. Cancer Chemother Pharmacol 67:285–291PubMedCrossRefGoogle Scholar
  31. 31.
    Liang Y, Hou M, Kallab AM, Barrett JT, El Etreby F, Schoenlein PV (2003) Induction of antiproliferation and apoptosis in estrogen receptor negative MDA-231 human breast cancer cells by mifepristone and 4-hydroxy-tamoxifen combination therapy: a role for TGF beta1. Int J Oncol 23:369–380PubMedGoogle Scholar
  32. 32.
    Perry RR, Kang Y, Greaves BR (1995) Relationship between tamoxifen-induced transforming growth factor beta 1 expression, cytostasis and apoptosis in human breast cancer cells. Br J Cancer 72:1441–1446PubMedCrossRefGoogle Scholar
  33. 33.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomized trials. Lancet 378, 9793:771–784. doi: 10.11016/S0140-6736(11)60993-8 Google Scholar
  34. 34.
    Desta Z, Ward BA, Soukhova NV, Flockhart DA (2004) Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A4 and CYP2D6. J Pharmacol Exp Ther 310:1062–1075PubMedCrossRefGoogle Scholar
  35. 35.
    Szliszka E, Helewski KJ, Mizgala E, Krol W (2011) The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells. Int J Oncol 39(4):771–779PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sibylle Abarzua
    • 1
    Email author
  • Tatsuo Serikawa
    • 1
  • Marlen Szewczyk
    • 2
  • Dagmar-Ulrike Richter
    • 2
  • Birgit Piechulla
    • 1
  • Volker Briese
    • 2
  1. 1.Department of Biochemistry, Faculty of Natural Sciences, Institute of Biological SciencesUniversity of RostockRostockGermany
  2. 2.Department of Obstetrics and Gynaecology, Faculty of MedicineUniversity of RostockRostockGermany

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