Antitumor Activities of Extract of Viscum album var. coloratum Modified with Viscum album var. coloratum Agglutinin

  • Lyu, Su-Yun (College of Natural Sciences, Seoul Women's University) ;
  • Rhim, Jee-Young (College of Natural Sciences, Seoul Women's University) ;
  • Moon, You-Sun (College of Natural Sciences, Seoul Women's University) ;
  • Jung, Seung-Hee (College of Natural Sciences, Seoul Women's University) ;
  • Lee, Kyue-Yim (College of Natural Sciences, Seoul Women's University) ;
  • Park, Won-Bong (College of Natural Sciences, Seoul Women's University)
  • Published : 2002.12.01


The mistletoe lectins are major active components in the extract of European mistletoe (Viscum album L) that have been widely used in adjuvant chemotherapy of cancer. This study was performed to investigate the antitumor activity of extract of Korean mistletoe (Viscum album var. coloratum) modified with Korean mistletoe lectin (Viscum album var. coloratum agglutinin, VCA). Compared with the results of VCA, survival rate was increased and experimental lung metastasis was reduced by treatment of modified extract (VCM). In addition, the treatment of VCM reduced angiogenesis and VCA-induced toxicity measured by a CAM assay. And VCM inhibited proliferation and induced apoptosis in vitro in tumor cells originated from tissues which are possible to apply topically without surgery. Taken together, the antitumor activities of VCM-treated group outperformed the activities of the VCA-treated group.


  1. Arends, M. J., Mcgregor, A. H., and Wyllie, A. H., Apoptosis is inversely related to necrosis and determines the growth in tumors bearing constitutively expressed myc, ras, and HPV oncogenes. J. Pathol., 144, 1045-1057 (1994)
  2. Bantel, H., Engels, I. H., Voelter, W., Schulze-Osthoff, K., and Wesselborg, S., Mistletoe lectin activates caspase-8/FLICE independently of death receptor signaling and enhances anticancer drug-induced apoptosis. Cancer Res., 59, 2083-2090 (1999)
  3. Brem, S., Brem, H., Folkman, J., Fmkelstein, D., Patz, A., Prolonged tumordormancy by prevention of neovascularization in Ihe vitreous. Cancer Res., 36, 2807-2812 (1976)
  4. B$\"u$ssing, A., Induction of apoptosis by the mistletoe lectins. A review on the mechanisms of cytotoxicity mediated by Viscum album L. Apoptosis, 1, 25-32 (1996)
  5. B$\"u$ssing, A., Vervecken, W., Wagner, M., Pf$\"u$ller, U., and Schietzel, M., Expression of mitochondrial Apo2.7 molecules and caspase3 activation in human lymphocytes treated with the ribosomeinhibiting mistletoe lectins and the cell membrane permeabilizing viscotoxins. Cytometry, 37, 133-139 (1999)<133::AID-CYTO6>3.0.CO;2-A
  6. B$\"u$ssing, A., Biological and pharmacological properties of Viscum album L.; From tissue flask to man. In A. B$\"u$ssing (eds.), Mistletoe, genus Viscum & other genera, Medicinal and aromatic ptantslndusirial profiles. Harwood Academic Publishers, Netherland, pp. 45-60, 2000
  7. Green, D. R. and Martin, S. J., The killer and the executioner: how apoptosis controls malignancy. Curr. Opin. ImmunoI., 7, 694-703 (1995)
  8. Hanahan, D., Folkman, J., Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. CeII, 86, 353-364 (1996)
  9. Kerr, J. F. R., Winterford, C. M., and Harmon, B. V., Apoptosis - its significance in cancer and cancer therapy. Cancer, 73, 2013-2026 (1994)<2013::AID-CNCR2820730802>3.0.CO;2-J
  10. Lyu, S. Y., Park, S. M., Choung, B. Y., and Park, W. B., Comparative study of Korean (Viscum album, var. coloratum) and European mistletoes (Viscum album). Arch. Pharm. Res., 23, 592-598 (2000)
  11. Lyu, S. Y., Park, W. B., Choi, K. H., and Kim, W. H., Involvement of caspase-3 in apoptosis induced by Viscum album var. coloratum agglutinin in HL-60 cells. Biosci. Biotechnol. Biochem., 65, 534-541 (2001)
  12. Lyu, S. Y., Choi, S. H., and Park, W. B., Korean mistletoe lectininduced apoptosis in hepatocarcinoma cells is associated with inhibition of telomerase via mitochondrial controlled pathway independent of p53. Arch. Pharm. Res., 25, 93-101 (2002)
  13. O'Reilly, M. S., Holmgren, L., Shing, Y., Chen, C., Rosenthal, R. A., Moses, M., Lane, W. S., Cao, Y., Sage, E. H., Folkman, J., Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell, 79, 315-328 (1994)
  14. Oikawa, T., Sasaki, T., Nakamura, M., Shimamura, M., Tanahashi, N., Omura, S., Tanaka, K. The proteasome is involved in angiogenesis. Biochem. Biophys. Res. Commun. 246, 243-248 (1998)
  15. Parangi, S., O'Reilly, M. S., Christofori, G., Lander, E., and Hanahan, D., Antiangiogenic therapy of transgenic mice impairs de nove tumor growth. Proc. Natl. Acad. Sci. USA. 93, 2002-2007 (1996)
  16. Park, W. B., Choung, B. Y., Park, S. M., Lee, T. S., Kim, J. H., and Ham, S. S., Antitumor activities of extracts and lectin from Viscum album L. and Viscum album var. coloratum on cultured HL-60 cells. Food Sci. Biotechnol., 8, 232-237 (1999a)
  17. Park, W. B., Choung, B. Y., Park, S. M., Kim, H. S., and Lyu, S. Y., Effects of drying process of mistletoes on cytotoxicities against cultured HL-60 and Molt-4 cells, Food Sci. Biotechnol., 8, 391-396 (1999b)
  18. Park, W. B., Lyu, S. Y., Kim, J. H., Choi, S. H., Chung, H. K., Ahn, S. H., Hong, S. Y., Yoon, T. J., and Choi, M. J., Inhibition of tumor growth and metastasis by korean mistletoe lectin is associated with apoptosis and antiangiogenesis. Cancer Biotherapy & Radiopharmaceuticals, 16, 439-447 (2001)
  19. Schwartz, L. M. and Osborn, B. A., Programmed cell death, apoptosis and killer genes. Immunol.Today, 14, 582-590 (1993)
  20. Stumpf, C. and B$\"u$ssing, A., Stimulation of antitumor immunity by intrapleural instillation of a Viscum album L. extract. Anti-Cancer Drugs, 8 (suppl 1), S23-S26 (1997)
  21. Sunamura. M.. Sun. L.. Lozonschi. L.. Duda. D. G.. Kodama. T.. Matsumoto, G., Shimamura, H., Takeda, K., Kobari, M., Hamada, H., Matsuno, S., The antiangiogenesis effect of interleukin 12 during early growth of human pancreatic cancer in SCID mice. Pancreas, 20, 227-233 (2000)
  22. Yokoda J., Tumor progression and metastasis. Carcinogenesis, 21, 497-503 (2000)
  23. Yoon, T. J., Yoo, Y. C., Choi, 0. B., Do, M. S., Kang, T. B., Lee, S. W., Azuma, I., Kim, J. B., Inhibitory effect of Korean mistletoe (Viscum album coloratum) extract on tumour angiogenesis and metastasis of haematogenous and non-haematogenous tumour cells in mice. Cancer Lett., 97, 83-91 (1995)
  24. Yoon, T. J., Yoo, Y. C., Kang, T. B., Y. J., Huh, C. S., Song, S. K., Lee, K. H., Azuma, I., 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)
  25. Yoon, T. J., Yoo, Y. C., Kang, T. B., Shimazki, 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)
  26. Filder, I. J., Cancer metastasis. Br. Med. Bull., 47, 157-162 (1991).