Immunomodulatory Activity of Protein-Bound Polysaccharide Extracted from Gheiidonium majus

  • Yun, Yeon-Sook (Laboratory of Immunology, Korea Cancer Hospital KAERI) ;
  • Song, Jie-Young (Laboratory of Immunology, Korea Cancer Hospital KAERI) ;
  • Yang, Hyun-Ok (Department of Traditional Medicines, Asan Institute for Life Sciences, Ulsan University) ;
  • Pyo, Suhk-Neung (Laborztory of Immunology, College of Pharmacy, SungKyunKwan University) ;
  • Jung, In-Sung (Laboratory of Immunology, Korea Cancer Hospital KAERI) ;
  • Yi, Seh-Yoon (Laboratory of Immunology, Korea Cancer Hospital KAERI)
  • Published : 2002.04.01

Abstract

In the course of searching immunomodulators from natural sources, the protein-bound polysaccharide, CM-Ala, has been isolated from the water extract of Chelidonium majus L. (Papaveraceae). The immunostimulatory characteristics have been investigated in several experiments such as generation of activated killer (AK) cells, proliferation of splenocytes, activation of macrophages and granulocyte macrophage-colony forming cell (GM-CFC) assay. Of the fractions obtained using Sephacryl S200 column chromatography, CM-Ala was the most effective fraction that augmented the cytotoxicity against Yac-1 tumor cells from 0.88% to 34.18% by culturing with splenocytes for 5 days. CM-Ala also enhanced nitric oxide production by two fold in peritoneal macrophages and exhibited antitumor activity. It showed mitogenic activity on both spleen cells and bone marrow cells. CM-Ala induced proliferation of splenocytes by 84 fold and increased GM-CFC numbers by 1.48 fold over than the non-treated. On the contrary, CM-Ala had cytotoxic activity to a diverse group of tumor cells. From the above results, we proposed that CM-Ala has a possibility of an effective antitumor immunostimulator.

Keywords

References

  1. Bradford, M. M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 72, 248-254 (1976) https://doi.org/10.1016/0003-2697(76)90527-3
  2. Chihara, G., Hamuro, J., Maeda, Y. Y., Arai, Y., and Fukuoka, F., Fractionation and purification of the polysaccharides with marked antitumor activity, especially lentinan, from Lentinus edodes (Berk) Sing. (an Edible mushroom). Cancer Res., 30, 2776-2781 (1970)
  3. Dimler, R. J., Schaefer, W. C., Wise, C. S., and Rist, C. E., Quantitative paper chromatography of D-glucose and its oligosaccharides. Anal. Chem., 24,1411-1415 (1952) https://doi.org/10.1021/ac60069a010
  4. Ghaffar, A., Cullen, R. T., and Woodruff, M.F.A., Further analysis of the anti-tumor effect in vitro of peritoneal exudate cells from mice treated with Corynebacterium parvum. Brit. J. Cancer, 31, 15-24 (1975) https://doi.org/10.1038/bjc.1975.3
  5. 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 2activated autologous human peripheral blood lymphocytes. J. Exp. Med.,155, 1823-1841 (1982) https://doi.org/10.1084/jem.155.6.1823
  6. Herbermann, R. B., Biological response modifiers for the treatment of cancer. In: E. Tsubura, I. Urashizaki, T. Aoki, S. Sone and Y. Kaneto. (Eds.). Rationale of Biological response Modifiers in Cancer Treatment. Excepta Medica, Princeton, pp. 240-255, (1985)
  7. Hibbs, J. B., Taintor, R. R., and Vavrin, Z., Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogrn oxidation to nitrite. Science, 235, 473-476 (1987) https://doi.org/10.1126/science.2432665
  8. Hibbs, J. B., Taintor, R. R., Vavrin, Z., and Rachlin, E. M., Nitric oxide; a cytotoxic-activated macrophage effector molecule. Biochem. Bioph. Res. Co., 157, 87-94 (1988) https://doi.org/10.1016/S0006-291X(88)80015-9
  9. Hoshina, T. and Uchida, A., OK-432 (picibanil): Property, action and chemical effectiveness. In: T. Hoshino. (Eds.), Excepta Medica, Amsterdam. pp. 3-21, (1984)
  10. Jee, H. J. and Lee, S. I., Implication of Korean medicinal plants. Korea medical Index Inc., Seoul, pp. 153, (1988)
  11. Kery, A., Horvath, J., Nasz, I., Verzar-petri, G., Kulcsar, G., and Dan, P., Antiviral alkaloids in Chelidonium majus. Acta Pharm. Hungarica, 57, 19-25 (1987)
  12. Kim, K. H., Lee, Y. S., Jung, I. S., Park, S. Y., Chung, H. Y., Lee, I. R., and Yun, Y. S., Acidic polysaccharide from Panax ginseng, Ginsan, induces Th1 cell and macrophage cytokines and generate LAK cells in synergy with rIL-2. Planta Med., 64, 110-115 (1998) https://doi.org/10.1055/s-2006-957385
  13. Klimetzek, V. and Remold, H.G., The murine bone marrow macrophage, a sensitive indicator cell for murine migration inhibitory factor and a new method for their harvest. Cell. Immunol. 53, 257-266 (1980) https://doi.org/10.1016/0008-8749(80)90327-5
  14. Lee, Y. S., Jung, I. S., Lee, I. R., Kim, K. H., Hong, W. S., and Yun, Y. S., Activation of multiple effector pathway of immune system by the antineoplastic immunostimulator acidic polysaccharide Ginsan isolated from Panax ginseng. Anticancer Res., 17, 323-332 (1997)
  15. Lenfeld, J., Kroutil, M., Marsalek, E, Slavik, J., Preininger, V.. and Simanek V., Antiinflammatory activity of quarternary benzophenanthridine alkaloids from Chelidonium majus. Planta Med., 43, 161-165 (1981) https://doi.org/10.1055/s-2007-971493
  16. Liepins A. and Nowicky J. W., Activation of spleen cell lytic activity by the alkaloid thiophosphoric acid derivative: ukrain. Int. J. Immunopharmaco., 14, 1437-1442 (1992) https://doi.org/10.1016/0192-0561(92)90016-E
  17. Lotze, M. T., Frana, L. W., Sharrow, S. O., Robb, R. J., and Rosenberg, S. A., In vivo administration of purified human interleukin 2. I. Half-life and immunologic effects of Jurkat cell line-derived interleukin 2. J. Immunol., 134, 157-166 (1985)
  18. Lotze, M. T., Grimm, E. A., Mazumder, A., Strausser, J. L., and Rosenberg, S. A., Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res., 41, 4420-4425 (1981)
  19. Lotze, M. T., Matory, Y. L., Rayner, A. A., Ettinghausen, S. E., Vetto, J. T., Seipp, CA, and Rosenberg, S.A., Clinical effects and toxicity of interleukin 2 in patients with cancer. Cancer Res., 58, 2764-2772 (1986)
  20. Lowry, O. H., Rosenberg, N. J., Farr, A. L., and Randall, R. J., Protein measurement with the folin phenol reagent. J. Biol. Chem., 193,265-275 (1951)
  21. Mule, J. J. and Rosenberg, S. A. , Measurement of cytotoxic activity of LAK/NK cells. In: J.E Coliga, AM. Kruisbeek, D.H. Margalies, E.M. Shevach and W. Strober.(Eds.). Current protocols in immunology. John Willey and Sons, New York, pp 7.18.1-7.18.7, (1991)
  22. Rosenberg, S. A., Lotze, M. T., Muul, L. M., Leitman, S., Chang, A. E., Ettinghausen, S. E., Maltory, Y. L., Skibber, J. M., Shiloni, E., and Vetto, J. T., Observations or the systemic administraion of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. New Engl. J. Med. 313,1485-1492 (1985)
  23. Rosenstein, M., Yron, I., Kaufman, Y., and Rosenberg, S. A., Lymphokine-activated killer cell: Lysis of fresh syngeneic natural killerresistant murine tumor cells by lymphocytes cultured in interleukin 2. Cancer Res., 44,1946-1953 (1984)
  24. Song, J. Y., Yang, H. O., Park, S. Y., Pyo, S. N., Kim, K. W. Son E. W., and Yun, Y. S., Screening of antineo-plastic immunomodulator from herbal medicines. Yakhak Hoeji, 42, 132-139 (1998)
  25. Talmadge, J. E. and Herbermann, R. B., The preclinical screening laboratory:Evaluation of lmmunomodulatory and therapeutic properties of biological response modifiers, Cancer Treat. Reports, 70, 171-182 (1986)
  26. Terry, W. D. and Rosenberg, S. A., Immunotherapy of Human Cancer. Elsevier North-Holland. New York, (1982)
  27. Tsukagoshi, S., Hashimoto, Y, Fujii, G., Kobayashi, H., Nomoto, K. and Orita, K., Krestin(PSK), Cancer Treat. Rev., 11, 131-155 (1984)
  28. Urba, W. J. and Longo, D. L., a-Interferon in the treatment of modular lymphoma. Semin. Oncol., 13 (suppl.5), 40-47 (1986)
  29. Voltchek, I., Kamyshentsev, M., Lavinsky, Y., Nowisky, J., Medvedev, Y., and Litvinchuk, L., Comparative study of the cytostatic effects of oliphen and ukrain. J Chemotherapy, 8, 144-146 (1996) https://doi.org/10.1179/joc.1996.8.2.144
  30. West, W. H., Tauer, K. W., Yannelli, J. R., Marshall, G. D., Orr, D. W., Thurman, G. B., and Oldham, R. K., Constant infusion recombinant interleukin 2 in adaptive immunotherapy of advanced cancer. New Engl. J Med., 316, 898-905(1987) https://doi.org/10.1056/NEJM198704093161502
  31. Wimer, B. M., The ideal biological response modifier. Mol. Biotherapy, 1, 311-317 (1989)
  32. Wyczolkowska, J., Michon, T., and Nowicky, J. W., Inhibitory effect of thiophosphoric acid alkaloid derivatives from Chelidonium majus (ukrain) on ovalbumin antigenicity and antiovalbumin IgE antibody response in mice. Drug. Exp. Clin. Res., 22, 225-228 (1996)