Abstract
Tangeretin, a flavonoid from citrus plants, was found to inhibit the invasion of MO4 cells (Kirsten murine sarcoma virus transformed fetal mouse cells) into embryonic chick heart fragmentsin vitro. The flavonoid appeared to be chemically stable in tissue culture medium, and the anti-invasive effect was reversible on omission of the molecule from the medium. Unlike (+)-catechin, another anti-invasive flavonoid, tangeretin bound poorly to extracellular matrix. It did not alter fucosylated surface glycopeptides of MO4 cells. Tangeretin seemed not to act as a microtubule inhibitor, as immunocytochemistry revealed no disturbance of the cytoplasmic microtubule complex. However, at antiinvasive concentrations of tangeretin, cell proliferation and thymidine incorporation appeared to be inhibited. When cultured on an artificial substrate, treated MO4 cells were less elongated, covered a larger surface area and exhibited a slower directional migration than untreated cells. From the decrease in ATP content in MO4 cells after tangeretin treatment, we deduce that this flavonoid inhibits a number of intracellular processes, which leads to an inhibition of cell motility and hence of invasion.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Ahmann, F. R., Garewal, H. S., Schifman, R., Celniker, A., andRodney, S., 1987, Intracellular adenosine triphosphate as a measure of human tumor cell viability and drug modulated growth.In Vitro Cellular and Developmental Biology,23, 474–480.
Billiau, A., Sobis, H., Eyssen, H., andVan den Berghe, H., 1973, Non-infectious intracisternal A-type particles in a sarcoma-positive, leukemia-negative mouse cell line transformed by murine sarcoma virus (MSV).Archiv für die gesamte Virusforschung,43, 345–351.
Bolscher, J. G. M., Schallier, D. C. C., Smets, L. A., van Rooy, H., Collard, J. G., Bruyneel, E. A., andMareel, M. M. K., 1986, Effect of cancer-related and drug-induced alterations in surface carbohydrates on the invasive capacity of mouse and rat cells.Cancer Research,46, 4080–4086.
Bracke, M. E., Castronovo, V., Van Cauwenberge, R. M.-L., Coopman, P., Vakaet, L., Jr, Strojny, P., Foidart, J.-M., andMareel, M. M., 1987, The anti-invasive flavonoid (+)-catechin binds to laminin and abrogates the effect of laminin on cell morphology and adhesion.Experimental Cell Research,173, 193–205.
Bracke, M. E., De Pestel, G., Castronovo, V., Vyncke, B., Foidart, J. M., Vakaet, L. C. A., andMareel, M. M., 1986, Flavonoids inhibit malignant tumor invasionin vitro.Plant Flavonoids in Biology and Medicine: Biological, Pharmacological and Structure-Activity Relationships, edited by V. Cody, E. Middleton, Jr, and J. B. Harborne (New York: Alan R. Liss).
Bracke, M. E., Van Cauwenberge, R. M.-L., andMareel, M. M., 1984, (+)-Catechin inhibits the invasion of malignant fibrosarcoma cells into chick heartin vitro.Clinical and Experimental Metastasis,2, 161–170.
Bracke, M. E., Van Cauwenberge, R. M. L., Mareel, M. M., Castronovo, V., andFoidart, J. M., 1986, Flavonoids: tools for the study of tumor invasionin vitro.Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological and Structure-Activity Relationships, edited by V. Cody, E. Middleton, Jr, and J. B. Harborne (New York: Alan R. Liss), pp. 441–444.
Bracke, M. E., Van Cauwenberge, R. M.-L., Storme, G., Coopman, P., Van Larebeke, N., andMareel, M. M., 1986, Action mechanisms of anti-invasive agents.Anticancer Research,6, 273–278.
De Mey, J., Hoebeke, J., De Brabander, M., Geuens, G., Joniau, M., 1977, Immunoperoxidase visualisation of microtubules and microtubular proteins.Nature (London),264, 273–275.
Fidler, I. J., Gersten, D. M., andHart, I. R., 1978, The biology of cancer invasion and metastasis.Advances in Cancer Research,28, 149–250.
Gabriel, D., 1982, Carbohydrates and receptor recognition.Hormone Receptors, edited by L. D. Kahn (New York: Wiley), pp. 137–156.
Gilfix, B. M., andSanwal, B. D., 1984, Relationship between cell surface asparagine-linked glycoproteins and myoblast differentiation. Analysis of wheat germ agglutinin-resistant mutants.Canadian Journal of Biochemistry and Cell Biology,62, 60–71.
Koehrle, J., Auf'mkolk, M., Spanka, M., Irmscher, K., Cody, V., andHesch, R.-D., 1986, Iodothyronine deiodinase is inhibited by plant flavonoids.Plant Flavonoids in Biology and Medicine: Biochemical Pharmacological and Structure-Activity Relationships, edited by V. Cody, E. Middleton, Jr, and J. B. Harborne (New York: Alan R. Liss), pp. 359–371.
Lawrence, W. D., Blas, S. D., andDavis, P. J., 1986, Sex-specific effect of quercetin on rabbit reticulocyte membrane Ca++-ATPase activity.Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological and Structure-Activity Relationships, edited by V. Cody, E. Middleton, Jr, and J. B. Harborne (New York: Alan R. Liss), pp. 273–276.
Liotta, L. A., 1985, Mechanisms of cancer invasion and metastasis.Important Advances in Oncology 1985, edited by V. T. De Vita, Jr, S. Hellman and S. A. Rosenberg (Philadelphia: J. B. Lippincott), pp. 28–41.
Liotta, L. A., 1986, Tumor invasion and metastases-Role of the extracellular matrix: Rhoads Memorial Award Lecture,Cancer Research,45, 1–8.
Liotta, L. A., Lee, C. W., andMorakis, D. J., 1980, New method for preparing large surfaces of intact human basement membrane for tumor invasion studies.Cancer Letters,11, 141–152.
Macander, P. J., 1986, Flavonoids affect acetylcholine, prostaglandin E2 and antigen-mediated smooth muscle contraction.Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological and Structure-Activity Relationships, edited by V. Cody, E. Middleton, Jr, and J. B. Harborne (New York: Alan R. Liss), pp. 489–492.
Mareel, M. M., 1982, The use of embryo organ cultures to study invasionin vitro.Tumor Invasion and Metastasis, edited by L. A. Liotta and I. R. Hart (The Hague, Boston, London: Martinus Nijhoff), pp. 207–230.
Mareel, M., 1983, Invasionin vitro: methods of analysis.Cancer Metastasis Reviews,2, 201–218.
Mareel, M., Bruyneel, E., De Bruyne, G., Dragonetti, C., andVan Cauwenberge, R., 1982, Growth and invasion: separate activities of malignant MO4 cell populationsin vitro.Membranes in Tumour Growth, edited by T. Galeotti, A. Cittadini, G. Neri and S. Papa (Amsterdam: Elsevier Biomedical Press), pp. 223–232.
Mareel, M., De Bruyne, G., Vandesande, F., andDragonetti, C., 1981, Immuno-histochemical study of embryonic chick heart invaded by malignant cells in three-dimensional culture.Invasion and Metastasis,1, 195–204.
Mareel, M. M., andDe Mets, M., 1984, Effect of microtubule inhibitors on invasion and on related activities of tumor cells.International Reviews on Cytology,90, 125–168.
Mareel, M. M., Dragonetti, C. H., Hooghe, R. J., andBruyneel, E. A., 1985, Effect of inhibitors of glycosylation and carbohydrate processing on invasion of malignant mouse MO4 cells in organ culture.Clinical and Experimental Metastasis,3, 197–207.
Mareel, M., Kint, J., andMeyvisch, C., 1979, Methods of study of the invasion of malignant C3H mouse fibroblasts into embryonic chick heartin vitro.Virchows Archiv (Cell Pathology),30, 95–111.
Martin, D. W., Jr, 1983, Glycoproteins, proteoglycans and glycosaminoglycans.Harper's Review of Biochemistry, edited by D. W. Martin, Jr, P. A. Mayer and V. W. Rodwell (Los Altos, CA: Lange Medical Publications), pp. 448–463.
McCarthy, J. B., Basara, M. L., Palm, S. L., Sas, D. F., andFurcht, L. T., 1985, The role of cell adhesion proteins-laminin and fibronectin-in the movement of malignant and metastatic cells.Cancer Metastasis Reviews,4, 125–135.
Meyvisch, C., 1983, Influence of implantation site on formation of metastases.Cancer Metastasis Reviews,2, 295–306.
Middleton, E., Jr., 1986, Effect of flavonoids on basophil histamine release and other secretory systems.Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological and Structure-Activity Relationships, edited by V. Cody, E. Middleton, Jr, and J. B. Harborne (New York: Alan Liss), pp. 493–506.
Middleton, E., Jr, Nairins, C., andFerriola, P., 1986, Effect of flavonoids on protein kinase C.Plant Flavonoids in Biology and Medicine: Biological, Pharmacological and Structure-Activity Relationships, edited by V. Cody, E. Middleton, Jr, and J. B. Harborne (New York: Alan R. Liss).
Mookerjee, B. K., Lee, T. P., Logue, G. P., Lippes, H. A., andMiddleton, E., 1986, The effects of flavonoids on human lymphocyte proliferative responses.Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological and Structure-Activity Relationship, edited by V. Cody, E. Middleton, Jr, and J. B. Harborne (New York: Alan R. Liss), pp. 511–520.
Nicolson, G. L., LaBiche, R. A., Frazier, M. L., Blick, M., Tressler, R. J., Reading, C. L., Irimura, T., andRotter, V., 1986, Differential expression of metastasis-associated cell surface glycoproteins and RNA in a murine large cell lymphoma.Journal of Cellular Biochemistry,31, 305–312.
Opdenakker, G., Van Damme, J., Bosman, F., Billiau, A., andDe Somer, P. (1986). Influence of carbohydrate side-chains on activity of tissue-type plasminogen activator.Proceedings of the Society for Experimental Biology and Medicine,182, 248–257.
Romeis, B., 1968,Mikroskopische Technik (Munich, Vienna: R. Oldenbourgh Verlag), pp. 703–704.
Russo, R. G., Thorgeirsson, U., andLiotta, L. A., 1982,In vitro quantitative assay of invasion using human amnion.Tumor Invasion and Metastasis, edited by L. A. Liotta and I. R. Hart (The Hague, Boston, London: Martinus Nijhoff), pp. 173–187.
Smets, L. A., andVan Beek, W. P., 1984, Carbohydrates of the tumor cell surface.Biochimica et Biophysica Acta,738, 237–249.
Storme, G., andMareel, M., 1980, Effect of anticancer agents on directional migration of malignant C3H mouse fibroblastic cellsin vitro.Cancer Research,40, 943–948.
Sträuli, P., andHaemmerli, G., 1984, The role of cancer cell motility in invasion.Cancer Metastasis Reviews,3, 127–141.
Thorgeirsson, U. P., Liotta, L. A., Kalebic, T., Margulies, I. M., Thomas, K., Rios-Candelore, M., andRusso, R. G., 1982, Effect of neutral protease inhibitors and a chemo-attractant on tumor cell invasionin vitro.Journal of the National Cancer Institute,69, 1049–1054.
Tomas-Barberan, F. A., andHostettmann, K., 1986, Antifungal flavonoids from the leaf surfaces ofHelichrysum nitens.Plant Flavonoids in Biology and Medicine: Biological, Pharmacological and Structure-Activity Relationships, edited by V. Cody, E. Middleton, Jr, and J. B. Harborne (New York: Alan R. Liss).
Van Beek, W. P., Smets, L. A., andEmmelot, P., 1973, Increased sialic acid density in surface glycoproteins of transformed and malignant cells-a general phenomenon?Cancer Research,33, 2913–2922.
Van Peteghem, M. C., andMareel, M. M., 1978, Alterations in shape, surface structure and cytoskeleton of HeLa cells during monolayer culture.Archives of Biology (Brussels),89, 67–87.
Verschueren, H., andVan Larebeke, N., 1984, A new model for the quantitative analysis of cell movementsin vitro: definition of a shape change factor.Cytometry,5, 557–561.
Wood, A. W., Smith, D. S., Chang, A. L., Huang, T.-T., andConney, A. H., 1986, Effects of flavonoids on the metabolism of xenobiotics.Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological and Structure-Activity Relationships, edited by V. Cody, E. Middleton, Jr, and J. B. Harborne (New York: Alan R. Liss), pp. 195–210.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bracke, M.E., Vyncke, B.M., Van Larebeke, N.A. et al. The flavonoid tangeretin inhibits invasion of MO4 mouse cells into embryonic chick heartin vitro . Clin Exp Metast 7, 283–300 (1989). https://doi.org/10.1007/BF01753681
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01753681