Skip to main content

Advertisement

Log in

Regulation of zinc transporters by dietary flaxseed lignan in human breast cancer xenografts

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Zinc is essential for cell growth. Previous studies have shown that zinc concentration in breast cancer tissues is higher than that in normal breast tissues. Zinc cannot passively diffuse across cell membranes and specific zinc transporter proteins are required. Two gene families have been identified involved in zinc homeostasis. ZnT transporters reduce intracellular zinc while ZIP transporters increase intracellular zinc. In this study, three human zinc transporter members: ZnT-1, ZIP2 and LIV-1 were chosen. We aimed to determine the effect of flaxseed lignan on the growth of ER-negative breast cancer cells in a nude mice model and observe the effect of flaxseed lignan on the regulation of the three zinc transporter in mRNA level. Nude mice were xenografted with human breast cancer cell line MDA-MB-231 and 6 weeks later were fed either the basal diet (BD) or BD supplemented with 10% FS and SDG for 5 weeks. The SDG levels were equivalent to the amounts in the 10% FS. RT-PCR was performed. Compared with the BD group, the tumor growth rate was significantly lower (P < 0. 05) in the FS and SDG group. ZnT-1 mRNA level in mammary tumor was increased in SDG group and decreased in FS group, but no significant difference was found. Extremely low amplification of ZIP2 from mRNA was detected, with no difference between the treatment groups. LIV-1 mRNA expression of SDG group increases compared with BD group. In FS group, it significantly increases nearly 9 times than that in BD group (P < 0. 005).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Mills BJ, Broghamer WL, Higgins PJ, Lindeman RD (1984) Inhibition of tumor growth by zinc depletion of rats. J Nutr 114:746–752

    PubMed  CAS  Google Scholar 

  2. Santoliquido PM, Southwick HW, Olwin JH (1976) Trace metal levels in cancer of the breast. Surg Gynecol Obstet 142:65–70

    PubMed  CAS  Google Scholar 

  3. Lee R, Woo W, Wu B et al (2003) Zinc accumulation in N-methyl-N-nitrosourea-induced rat mammary tumors is accompanied by an altered expression of ZnT-1 and metallothionein. Exp Biol Med (Maywood) 228(6):689–696

    CAS  Google Scholar 

  4. Thomoson LU (1995) Flaxseed, lignans, and cancer. In: Cunnane SC, Thomoson LU (eds) Flaxseed in human nutrition. AOCS Press, Champaign, IL, pp 219–236

    Google Scholar 

  5. Nebe B, Peters A, Duske K et al (2006) Influence of phytoestrogens on the proliferation and expression of adhesion receptors in human mammary epithelial cells in vitro. Eur J Cancer Prev 15(5):405–415

    Article  PubMed  CAS  Google Scholar 

  6. Serraino M, Thompson LU (1992) The effect of flaxseed supplementation on the initiation and promotional stages of mammary tumorigenesis. Nutr Cancer 17(2):153–159

    Article  PubMed  CAS  Google Scholar 

  7. Thompson LU, Rickard SE, Orcheson LJ et al (1996) Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis. Carcinogenesis 17(6):1373–1376

    Article  PubMed  CAS  Google Scholar 

  8. Rickard SE, Yuan YV, Chen J, Thompson LU (1999) Dose effects of flaxseed and its lignan on N-methyl-N-nitrosourea-induced mammary tumorigenesis in rats. Nutr Cancer 35(1):50–57

    Article  PubMed  CAS  Google Scholar 

  9. Chen J, Stavro PM, Thompson LU (2002) Dietary flaxseed inhibits human breast cancer growth and metastasis and downregulates expression of insulin-like growth factor and epidermal growth factor receptor. Nutr Cancer 43(2):187–192

    Article  PubMed  CAS  Google Scholar 

  10. Wang L, Chen J, Thompson LU (2005) The inhibitory effect of flaxseed on the growth and metastasis of estrogen receptor negative human breast cancer xenograftsis attributed to both its lignan and oil components. Int J Cancer 116(5):793–798

    Article  PubMed  CAS  Google Scholar 

  11. Kitts DD, Yuan YV, Wijewickreme AN, Thompson LU (1999) Antioxidant activity of the flaxseed lignan secoisolariciresinol diglycoside and its mammalian lignan metabolites enterodiol and enterolactone. Mol Cell Biochem 202(1–2):91–100

    Article  PubMed  CAS  Google Scholar 

  12. Prasad K (2000) Antioxidant activity of secoisolariciresinol diglucoside-derived metabolites, secoisolariciresinol, enterodiol, and enterolactone. Int J Angiol 9(4):220–225

    Article  PubMed  Google Scholar 

  13. Rajesha J, Murthy KN, Kumar MK et al (2006) Antioxidant potentials of flaxseed by in vivo model. J Agric Food Chem 54(11):3794–3799

    Article  PubMed  CAS  Google Scholar 

  14. Hirano T, Fukuoka K, Oka K et al (1990) Antiproliferative activity of mammalian lignan derivatives against the human breast carcinoma cell line, ZR-75-1. Cancer Invest 8(6):595–602

    Article  PubMed  CAS  Google Scholar 

  15. Farina HG, Pomies M, Alonso DF, Gomez DE (2006) Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer. Oncol Rep 16(4):885–891

    PubMed  CAS  Google Scholar 

  16. Kambe T, Yamaguchi-Iwai Y, Sasaki R et al (2004) Overview of mammalian zinc transporters. Cell Mol Life Sci 61(1):49–68 Review

    Article  PubMed  CAS  Google Scholar 

  17. Gaither LA, Eide DJ (2001) Eukaryotic zinc transporters and their regulation. Biometals 14(3–4):251–270 Review

    Article  PubMed  CAS  Google Scholar 

  18. Beyersmann D, Haase H (2001) Functions of zinc in signaling, proliferation and differentiation of mammalian cells. BioMetals 14:331–341

    Article  PubMed  CAS  Google Scholar 

  19. Vallee BL, Falchuk KH (1993) The biochemical basis of zinc physiology. Physiol Rev 73:79–118

    PubMed  CAS  Google Scholar 

  20. Michael JD, Teresa MM, Arnold H et al (2000) Metalloproteinases: role in breast carcinogenesis, invasion and metastasis. Breast Cancer Res 2:252–257

    Article  Google Scholar 

  21. Palmiter RD, Findley SD (1995) Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc. EMBO J 14:639–649

    PubMed  CAS  Google Scholar 

  22. Franklin RB, Ma J, Zou J, Guan Z, Kukoyi BI et al (2003) Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells. J Inorg Biochem 96:435–442

    Article  PubMed  CAS  Google Scholar 

  23. Manning DL, Daly RJ, Lord PG, Kelly KF, Green CD (1988) Effects of oestrogen on the expression of a 4.4 kb mRNA in the ZR-75-1 human breast cancer cell line. Mol Cell Endocrinol 59:205–212

    Article  PubMed  CAS  Google Scholar 

  24. Fong LY, Mancini R, Nakagawa H, Rustgi AK, Huebner K (2003) Combined cyclin D1 overexpression and zinc deficiency disrupts cell cycle and accelerates mouse forestomach carcinogenesis. Cancer Res 63:4244–4252

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. P. Winterhalter and Melanie Stuertz for the pure standards of SDG.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lian-ying Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, Ly., Wang, Xl., Sun, Dx. et al. Regulation of zinc transporters by dietary flaxseed lignan in human breast cancer xenografts. Mol Biol Rep 35, 595–600 (2008). https://doi.org/10.1007/s11033-007-9129-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-007-9129-8

Keywords

Navigation