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Antitumor activity of the Korean Mistletoe Lectin is attributed to activation of macrophages and NK cells

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Abstract

Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM;Viscum album coloratura) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 lymphoma cells) was investigated in syngeneic mice. An intravenous (i.v.) administration of KML-C (20-50 ng/mouse) 2 days before tumor inoculation significantly inhibited lung metastases of both B16-BL6 and colon 26-M3.1 cells. The prophylactic effect of 50 ng/mouse of KML-C on lung metastasis was almost the same with that of 100 μg/mouse of KM. Treatment with KML-C 1 day after tumor inoculation induced a significant inhibition of not only the experimental lung metastasis induced by B16-BL6 and colon 26-M3.1 cells but also the liver and spleen metastasis of L5178Y-ML25 cells. Furthermore, multiple administration of KML-C given at 3 day-intervals after tumor inoculation led to a significant reduction of lung metastasis and suppression of the growth of B16-BL6 melanoma cells in a spontaneous metastasis model. In an assay for natural killer (NK) cell activity, i.v. administration of KML-C (50 ng/mouse) significantly augmented NK cytotoxicity against Yac-1 tumor cells 2 days after KML-C treatment. In addition, treatment with KML-C (50 ng/mouse) induced tumoricidal activity of peritoneal macrophages against B16-BL6 and 3LL cells. These results suggest that KML-C has an immunomodulating activity to enhance the host defense system against tumors, and that its prophylactic and therapeutic effect on tumor metastasis is associated with the activation of NK cells and macrophages.

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References

  • Andreesen, R., Scheibenbogen, C., Brugger, W., Krause, S., Meerpohl, H. G., Leser, H. G., Engler, H., and Lohr, G. W., Adoptive transfer of tumor cytotoxic macrophages generatedin vitro from curculating monocytes: a new approach to cancer immunotherapy.Cancer Res., 50, 7450–7456 (1990).

    PubMed  CAS  Google Scholar 

  • Barlozzari, T. J., Leonhardt, R. H., Wiltrout, R. B., Herberman, R. B., and Reynolds, C. W., Direct evidence for the role of LGL in the reduction of experimental metastasis.J. Immunol., 134, 2783–2789 (1985).

    PubMed  CAS  Google Scholar 

  • Bloksma, N., Dijk, H. V., Korst, P., and Willers, J. M., Cellular and humoral adjuvant activity of Mistletoe extract.Immunobiol., 156, 309–319 (1979).

    CAS  Google Scholar 

  • Franz, H., Mistletoe lectins and their A & B chains.Oncology, 43: suppl. 1, 23–28 (1986).

    PubMed  CAS  Google Scholar 

  • Gilles, R. G., Jung, M. L., Dominique, D. S., and Beck, J. P., Comparison of the effects of fermented and unfermented mistletoe preparations on cultured tumor cells.Oncology, 43: suppl 1, 35–41 (1986).

    Google Scholar 

  • Grimm, E. A., Mazumder, A., Zhang, H. Z., and Rosenberg, S. A., Lymphokine-activated killer cell phenomenon: Lysis of natural killer resistant fresh solid tumor cells by interleikin-2 activated autologous human peripheral blood lymphocytes.J. Exp. Med., 155, 1823–1841 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Hajto, T., Immunomodulatory effect of Iscador: a Viscum album preparation.Oncology 43: suppl 1, 51–61 (1986).

    Article  PubMed  Google Scholar 

  • Hajto, T., Hostanska, K., Frei, K., Rordorf, C. and Gabius, H. J., Increased secretion of tumour necrosis factor-α, interleukin 1, and interleukin 6 by human mononuclearcells exposed to β-galactoside lectin from clinically applied mistletoe extract.Cancer Res., 50, 3322–3326 (1990).

    PubMed  CAS  Google Scholar 

  • Hamprecht, K., Handgretinger, R., Voetsch, W., and Anderer, F. A., Mediation of human NK-activity by component in extracts of Viscum album.Int. J. Immunopharmacol., 9, 199–209 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Hanna, N., The role of natural killer cells in control of tumor growth and metastasis.Biochim. Biophys. Acta, 780, 2132–2630 (1985).

    Google Scholar 

  • Hayakawa, Y, Fujii, H., Hase, K., Ohnishi, Y., Sakukawa, R., Kadota, S., Namba, T., and Saiki, I., Anti-metastatic and immunomodulating properties of the water extract from Celosia argentea seeds.Bio. Pharm. Bull., 21, 1154–1159 (1998).

    CAS  Google Scholar 

  • Herberman, R. B., Possible role of natural killer cells and other effector cells in immune surveillance against cancer.J. Invest. Dermatol., 83: suppl 1, 137–140 (1984).

    Article  Google Scholar 

  • Hulsen, H., Kron, R., and Mechelke, F., Influence of Viscum album preparations on the natural killer cell-mediated cytotoxicity of peripheral blood.Naturwissenschaften, 76, 530–531 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Kuttan, G., Vasudevan, D. M., and Kuttan, R., Effect of a preparation from Viscum album an on tumor developmentin vitro and in mice.J. Ethnopharmacology, 29, 35–41 (1990).

    Article  CAS  Google Scholar 

  • Kuttan, G. and Kuttan, R., Immunological mechanism of action of the tumor reducing peptide from mistle extract (NSC 635089) cellular proliferation.Cancer Letters, 66, 123–130 (1992a).

    Article  PubMed  CAS  Google Scholar 

  • Kuttan, G. and Kuttan, R., Immunomodulatory activity of a peptide isolated from Viscum album extract (NSC 635089).Immunological Investigations, 21, 285–296 (1992b).

    Article  PubMed  CAS  Google Scholar 

  • Khwaja, T. A., Varven, J. C., Pentescost, S., and Pande, H., Isolation of biologically active alkaloids from Korean mistletoe Viscum album, coloratum.Experientia, 36, 599–600 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Mannel, D. N., Becker, H., Gundt, A., Kist, A., and Franz, H., Induction of tumour necrosis factor expression by a lectin from Viscum album.Cancer Immunol. Immunother, 33, 177–182 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Mertzer, G., Franz, H., Kindt, A., Fahlbusch, B., and Sus, J., Thein vitro activity of lectin 1 from mistletoe (ML 1) and its isolated A and B chains in functions of macrophages and polymorphonuclear cells.Immunobiol., 169, 461–471 (1985).

    Google Scholar 

  • Mueller, E. A., Hamprecht, K., and Anderer, F. A., Biological characterization of a component in extract of Viscum album enhancing human NK cytotoxicity.Immunopharmacology, 17, 11–18 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Mueller, E. A. and Anderer, F. A., Chemical specificity of effector cell/tumor cell bridging by a Viscum album rhamnogalacturonan enhancing cytotoxicity of human NK cells.Immunopharmacology, 19, 69–77 (1990a).

    Article  PubMed  CAS  Google Scholar 

  • Mueller, E. A. and Anderer, F. A., Viscum album oligosaccharide activating human natural cytotoxicity is an interferon g inducer.Cancer Immunol. Immunother., 32, 221–227 (1990b).

    Article  PubMed  CAS  Google Scholar 

  • Mueller, F. A. and Anderer, F. A., Synergistic action of a plant rhamno-galacturonan enhancing antitumor cytotoxicity of human natural killer and lymphokine-activated killer cells: chemical specificity of target cell recognition.Cancer Res., 50, 3646–3651 (1990c).

    PubMed  CAS  Google Scholar 

  • Olsnes, S., Stirpe, F., Sandvig, K., and Pihl, A., Isolation and characterization of viscumin, a toxic lectin fromViscum album L. (mistletoe).J. Biol. Chem., 257, 13263–13270 (1982).

    PubMed  CAS  Google Scholar 

  • Pollack, S. B. and Hallenbeck, L. A.,In vivo induction of NK activity with anti-NK1 serum: direct evaluation of NK cells in tumor clearance.Int. J. Cancer, 29, 203–207 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Ribereau-Gayon, G., Jung, M. L, Di Scala, D., and Beck, J. P., Comparison of the effects of fermented and unfermented mistletoe preparations on cultured tumor cells.Oncology, 43: suppl. 1, 35–41 (1986).

    PubMed  CAS  Google Scholar 

  • Schantz, S. P., Brown, B. W., Lira, E., Taylor, D. L., and Beddingfield, N., Evidence for the role of natural immunity in the control of metastatic spread of head and neck cancer.Cancer Immnunol. Immunother., 25, 141–148 (1987).

    CAS  Google Scholar 

  • Stiefel, T. and Voelter, W., Complete amino acid sequence of the A chain of mistletoe lectin I.FEBS Lett., 399, 153–157 (1996).

    Article  PubMed  Google Scholar 

  • Yoo, Y. C., Saiki, I., Sato, K., and Azuma, I., MDP-Lys(L18), a lipophilic derivative of muramyl dipeptide, inhibits the metastasis of hematogenous and non-hematogenous tumors in mice.Vaccine, 12, 175–180 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Yoo, Y. C., Watanabe, S., Watanabe, R., Hata, K., Shimazaki, K., and Azuma, I., Bovine lactoferrin and lactoferricin, a peptide derived from bovine lactoferrin, inhibit tumor metastasis in mice.Jpn. J. Cancer Res., 88, 184–190 (1997).

    PubMed  CAS  Google Scholar 

  • Yoon, T. J., Yoo, Y. C., Hong, E. K., Cho, Y. H., Lee, S. W., Azuma, I., Yoo, B. I., and Kim, J. B., Effect of Korean mistletoe extract on the induction of IL-1 and TNF-a from mouse macrophages.Kor. J. Pharmacognosy, 25, 132–139 (1994).

    Google Scholar 

  • Yoon, T. J., Yoo, Y C., Choi, O. B., Do, M. S., Kang, T. B., Lee, S. W., Azuma, I., and Kim, J. B., Inhibitory effect of Korean mistletoe (Viscum album coloratum) extract on tumor angiogenesis and metastasis of haematogenous and non-haematogenous tumour cells in mice.Cancer Lett., 97, 83–91 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Yoon, T. J., Yoo, Y C., Kang, T B., Baek, Y J., Huh, C. S., Song, S. K., Lee, K. H., Azuma, I., and Kim, J. B., Prophylactic effect of Korean mistletoe (Viscum album coloratum) extract on tumor metastasis is mediated by enhancement of NK cell activity.Int. J. Immunopharmacol., 20, 163–172 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Yoon, T. J., Yoo, Y C., Kang, T. B., Shimazaki, K., Song, S. K., Lee, K. H., Kim, S. H., Park, C. H., Azuma, I. and Kim, J. B., Lectins isolated from Korean mistletoe (Viscum album coloratum) induce apoptosis in tumor cells.Cancer Lett., 136, 33–40 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Yoon, T. J., Yoo, Y C., Kang, T. B, Her, E., Kim, S. H., Kim, K., Azuma, I., and Kim, J. B., Cellular and humoral adjuvant activity of lectins isolated from Korean mistletoe (Viscum album coloratum).Int. Immunopharmacol., 1, 881–889 (2001).

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Jong Bae Kim.

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Yoon, T.J., Yoo, Y.C., Kang, T.B. et al. Antitumor activity of the Korean Mistletoe Lectin is attributed to activation of macrophages and NK cells. Arch Pharm Res 26, 861–867 (2003). https://doi.org/10.1007/BF02980033

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