Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Antitumor Activity of the Korean Mistletoe Lectin is Attributed to Activation of Macrophages and NK Cells

  • Yoon, Tae-Joon (Institute for Biomedical Research, Han Dong University) ;
  • Yoo, Yung-Choon (Department of Microbiology, College of Medicine, Konyang University) ;
  • Kang, Tae-Bong (Institute for Biomedical Research, Han Dong University) ;
  • Song, Seong-Kyu (Institute for Biomedical Research, Han Dong University) ;
  • Lee, Kyung-Bok (Department of Biochemistry, College of Medicine, Konyang University) ;
  • Her, Erk (Department of Immunology, College of Medicine, Kon-Kuk University) ;
  • Song, Kyung-Sik (School of Applied Biology and Chemistry, College of Agriculture and Life Science, Kyungpook National University) ;
  • Kim, Jong-Bae (Institute for Biomedical Research, Han Dong University)
  • Published : 2003.10.01
Download PDF
⟨ Previous Next ⟩

Abstract

Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26M3.1 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 $\mu$ g/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 26M3.1 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.

Keywords

References

  1. 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 generated in vitro from curculating monocytes: a new approach to cancer immunotherapy. Cancer Res., 50, 7450-7456 (1990)
  2. 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)
  3. Bloksma, N., Dijk, H. V., Korst, P., and Willers, J. M., Cellular and humoral adjuvant activity of Mistletoe extract. Immunobiol., 156, 309-319 (1979)
  4. Franz, H., Mistletoe lectins and their A & B chains. Oncology, 43 :suppl. 1, 23-28 (1986)
  5. 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) https://doi.org/10.1159/000226418
  6. 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) https://doi.org/10.1084/jem.155.6.1823
  7. Hajto, T., Immunomodulatory effect of Iscador: a Viscum album preparation. Oncology 43:suppl 1, 51-61 (1986) https://doi.org/10.1159/000226420
  8. Hajto, T., Hostanska, K., Frei, K., Rordorf, C. and Gabius, H. J., Increased secretion of tumour necrosis factor-$\alpha$, interleukin 1, and interleukin 6 by human mononuclearcells exposed to $\beta$-galactoside lectin from clinically applied mistletoe extract. Cancer Res., 50, 3322-3326 (1990)
  9. 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) https://doi.org/10.1016/0192-0561(87)90095-6
  10. Hanna, N., The role of natural killer cells in control of tumor growth and metastasis. Biochim. Biophys. Acta, 780, 2132-2630 (1985)
  11. 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) https://doi.org/10.1248/bpb.21.1154
  12. 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) https://doi.org/10.1111/1523-1747.ep12282012
  13. 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) https://doi.org/10.1007/BF00374131
  14. Kuttan, G., Vasudevan, D. M., and Kuttan, R., Effect of a preparation from Viscum album an on tumor development in vitro and in mice. J. Ethnopharmacology, 29, 35-41 (1990) https://doi.org/10.1016/0378-8741(90)90095-B
  15. 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) https://doi.org/10.1016/0304-3835(92)90224-J
  16. Kuttan, G. and Kuttan, R., Immunomodulatory activity of a peptide isolated from Viscum album extract (NSC 635089). Immunological Investigations, 21, 285-296 (1992b) https://doi.org/10.3109/08820139209069368
  17. 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) https://doi.org/10.1007/BF01965825
  18. 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)
  19. Mertzer, G., Franz, H., Kindt, A., Fahlbusch, B., and Sus, J., The in 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) https://doi.org/10.1016/S0171-2985(85)80002-4
  20. 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) https://doi.org/10.1016/0162-3109(89)90003-9
  21. 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) https://doi.org/10.1016/0162-3109(90)90028-D
  22. 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) https://doi.org/10.1007/BF01741704
  23. 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)
  24. Olsnes, S., Stirpe, F., Sandvig, K., and Pihl, A., Isolation and characterization of viscumin, a toxic lectin from Viscum album L. (mistletoe). J. Biol. Chem., 257, 13263-13270 (1982)
  25. 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) https://doi.org/10.1002/ijc.2910290215
  26. 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) https://doi.org/10.1159/000226418
  27. 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)
  28. Stiefel, T. and Voelter, W., Complete amino acid sequence of the A chain of mistletoe lectin I. FEBS Lett., 399, 153-157 (1996) https://doi.org/10.1016/S0014-5793(96)01309-9
  29. 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) https://doi.org/10.1016/0264-410X(94)90057-4
  30. 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) https://doi.org/10.1111/j.1349-7006.1997.tb00364.x
  31. 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)
  32. 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 nonhaematogenous tumour cells in mice. Cancer Lett., 97, 83-91 (1995) https://doi.org/10.1016/0304-3835(95)03956-W
  33. 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) https://doi.org/10.1016/S0192-0561(98)00024-1
  34. 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) https://doi.org/10.1016/S0304-3835(98)00300-0
  35. 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) https://doi.org/10.1016/S1567-5769(01)00024-8