The Citrus Methoxyflavone Tangeretin Affects Human Cell-Cell Interactions

  • Marc E. Bracke
  • Tom Boterberg
  • Herman T. Depypere
  • Christophe Stove
  • Georges Leclercq
  • Marc M. Mareel
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 505)

Abstract

Two effects of the citrus methoxyflavone tangeretin on cell-cell interactions are biologically relevant. Firstly, tangeretin upregulates the function of the E-cadherin/catenin complex in human MCF-7/6 breast carcinoma cells. This leads to firm cell-cell adhesion and inhibition of invasion in vitro. Secondly, tangeretin downregulates the interleukin-2 receptor on T-lymphocytes and natural killer cells. This leads to a decrease in the cytotoxic competence of these immunocytes against cancer cells. The second effect can become important when high doses of tangeretin are combined with adjuvant tamoxifen treatment for breast cancer. Experiments with nude mice bearing MCF-7/6 tumors showed that tangeretin given orally at high doses, abrogated the therapeutic suppression of tumor growth exerted by tamoxifen. No evidence for a tumor promoting effect of tangeretin by itself was found in these experiments. Tangeretin may be an interesting molecule for application in cases where immunosuppression could be clinically beneficial.

Keywords

Natural Killer Cell Lymphokine Activate Killer Combine Treatment Group Immune Defense System Chromium Release Assay 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bracke, M. E., Bruyneel, E. A., Vermeulen, S. J., Vennekens, K., Van Marck, V., and Mareel, M. M., 1994a, Citrus flavonoid effect on tumor invasion and metastasis, Food Technology 48: 121–124.Google Scholar
  2. Bracke, M. E., Charlier, C., Bruyneel, E. A., Labit, C., Mareel, M. M., and Castronovo, V., 1994b, Tamoxifen restores the E-cadherin function in human breast cancer MCF-7/6 cells and suppresses their invasive phenotype, Cancer Res. 54: 4607–4609.Google Scholar
  3. Bracke, M. E., Depypere, H. T., Boterberg, T., Van Marck, V. L., Vennekens, K. M., Vanluchene, E., Nuytinck, M., Serreyn, R. and Mareel, M. M., 1999, Influence of tangeretin on tamoxifen’s therapeutic benefit in mammary cancer, J. Nat!. Cancer Inst. 91: 354–359.CrossRefGoogle Scholar
  4. Kemler, R., 1992, Classical cadherins, Semin. Cell Biol. 3: 149–155.CrossRefGoogle Scholar
  5. Mareel, M., Berx, G., Van Roy, F., and Bracke, M., 1996a, Cadherin/catenin complex: a target for antiinvasive therapy? J. Cell Biochem. 61: 524–530.CrossRefGoogle Scholar
  6. Mareel, M., Noe, V., Vermeulen, S., and Bracke, M., 1996b, Anti-invasive therapy: manipulation of the E-cadherin/catenin/cytoskeleton complex, Anticancer Drugs 7 (Suppl 3): 149–156.Google Scholar
  7. Roitt, I., Brostoff, J., and Male, D., 1998, Cell-mediated immune reactions, In: Immunology, 5th Ed., Roitt, L, Brostoff, J., and Male, D., Eds., Mosby International Ltd, London, pp. 122–123.Google Scholar
  8. Vleminckx, K., Vakaet, L. Jr., Mareel, M., Fiers, W., and Van Roy, F., 1991, Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role, Cell 66: 107–119.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Marc E. Bracke
    • 1
  • Tom Boterberg
    • 1
  • Herman T. Depypere
    • 2
  • Christophe Stove
    • 1
  • Georges Leclercq
    • 3
  • Marc M. Mareel
    • 1
  1. 1.Laboratory of Experimental Cancerology, Department of Radiotherapy, Nuclear Medicine and Experimental CancerologyGhent University HospitalGentBelgium
  2. 2.Department of Gynecology and ObstetricsGhent University HospitalGentBelgium
  3. 3.Laboratory of Bacteriology and VirologyGhent University HospitalGentBelgium

Personalised recommendations