Table of Contents Author Guidelines Submit a Manuscript
Evidence-Based Complementary and Alternative Medicine
Volume 2011, Article ID 298972, 6 pages
http://dx.doi.org/10.1093/ecam/nep191
Review Article

Difficulties and Perspectives of Immunomodulatory Therapy with Mistletoe Lectins and Standardized Mistletoe Extracts in Evidence-Based Medicine

1Department of Immunology and Biotechnology, University of Pécs, Pécs, Hungary
2Department of Medical Chemistry, University of Pécs, Pécs, Hungary

Received 24 July 2009; Accepted 19 October 2009

Copyright © 2011 Tibor Hajtó et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. Hostanska, T. Hajto, K. Weber, J. Fisher, H. Lentzen, B. Sütterlin et al., “A natural immunity-activating plant lectin, Viscum album agglutinin-I, induces apoptosis in human lymphocytes, monocytes, monocytic THP-1 cells and murine thymocytes,” Nature Immunology, vol. 15, pp. 295–311, 1998. View at Google Scholar
  2. V. Lavastre, M. Pelletier, R. Saller, K. Hostanska, and D. Girard, “Mechanisms involved in spontaneous and Viscum album agglutinin-I —induced human neutrophil apoptosis: Viscum album agglutinin-I accelerates the loss of antiapoptotic Mcl-1 expression and the degradation of cytosceletal paxillin and vimentin proteins via caspases,” Journal of Immunology, vol. 168, pp. 1419–1427, 2002. View at Google Scholar
  3. K. Hostanska, V. Vuong, S. Rocha et al., “Recombinant mistletoe lectin induces p53-independent apoptosis in tumour cells and cooperates with ionising radiation,” British Journal of Cancer, vol. 88, no. 11, pp. 1785–1792, 2003. View at Publisher · View at Google Scholar · View at PubMed
  4. T. Hajto, T. Berki, F. Boldizsár, and P. Németh, “Galactoside-specific plant lectin, Viscum album agglutinin-I induces enhanced proliferation and apoptosis of murine thymocytes in vivo,” Immunology Letters, vol. 86, no. 1, pp. 23–27, 2003. View at Publisher · View at Google Scholar
  5. S. H. Choi, Y. L. Su, and B. P. Won, “Mistletoe lectin induces apoptosis and telomerase inhibition in human A253 cancer cells through dephosphorylation of Akt,” Archives of Pharmacal Research, vol. 27, no. 1, pp. 68–76, 2004. View at Google Scholar
  6. M. Harmsma, M. Gromme, M. Ummelen, W. Dingnef, K. J. Tusenius, and F. C. Ramaekers, “Differential effects of Viscum album extract Iscador Qu on cell cycle progression and apoptosis in cancer cells,” International Journal of Oncology, vol. 25, pp. 1521–1529, 2004. View at Google Scholar
  7. M. Harmsma, M. Gromme, M. Ummelen, W. Dingnef, K. J. Tusenius, and F. C. Ramaekers, “Effect of mistletoe (Viscum album L.) extracts Iscador on cell cycle and survival of tumor cells,” Drug Research, vol. 56, pp. 474–482, 2006. View at Google Scholar
  8. A. Savoie, V. Lavastre, M. Pelletier, T. Hajto, K. Hostanska, and D. Girard, “Activation of human neutrophils by the plant lectin Viscum album agglutinin-I: modulation of de novo protein synthesis and evidence that caspases are involved in induction of apoptosis,” Journal of Leukocyte Biology, vol. 68, no. 6, pp. 845–853, 2000. View at Google Scholar
  9. S. Elluru, J.-P. D. van Huyen, B. Wootla et al., “Tumor regressive effects of Viscum album preparations. Exploration of immunomodulatory mechanisms,” Medicina, vol. 67, supplement II, pp. 85–89, 2007. View at Google Scholar
  10. T. Hajto, K. Hostanska, and H.-J. Gabius, “Modulatory potency of the b-galactoside-specific lectin from mistletoe extract (Iscador) on the host defense system in vivo in rabbits and patients,” Cancer Research, vol. 49, pp. 4803–4808, 1990. View at Google Scholar
  11. T. Hajto, K. Hostanska, K. Frei, K. Rordorf, and H.-J. Gabius, “Increased secretion of tumor necrosis factor-α, interleukin-1 and interleukin-6 by human mononuclear cells exposed to β-galactoside-specific mistletoe lectin,” Cancer Research, vol. 50, pp. 3322–3326, 1990. View at Google Scholar
  12. T. Hajto, K. Hostanska, K. Weber, H. Zinke, J. Fischer, U. Mengs et al., “Effect of a recombinant lectin, Viscum album agglutinin (rVAA) on secretion of interleukin-12 in cultured human peripheral blood mononuclear cells and on NK-cell-mediated cytotoxicity of rat splenocytes in vitro and in vivo,” Nature Immunology, vol. 16, pp. 34–46, 1998. View at Google Scholar
  13. T. Hajto, K. Hostanska, T. Berki, F. Boldizsár, and P. Németh, “Oncopharmacological perspectives of a plant lectin (Viscum album agglutinin-I): overwiew of recent results from in vitro experiments and in vivo animal models, and their possible relevance for clinical applications,” Evidence-Based Complementary and Alternative Medicine, vol. 2, pp. 59–67, 2005. View at Google Scholar
  14. J. P. Duong van Huyen, S. Delignat, J. Bayry, M. D. Kzatchkine, P. Bruneval, A. Nicoletti et al., “Interleukin-12 is associated with the in vivo anti-tumor effect of mistletoe extracts in B16 mouse melanoma,” Cancer Letters, vol. 243, pp. 32–37, 2006. View at Google Scholar
  15. T. Hajto, K. Hostanska, M. Fornalski, and A. Kirsch, “Anti-tumor activity of an munomodulator: the beta-galactoside-specific mistletoe lectins given in mistletoe extracts (Iscador),” Deutsch Zschr Onkol, vol. 23, pp. 1–6, 1991. View at Google Scholar
  16. A. Kirsch, “Successful treatment of metastatic malignant melanoma with Viscum album extract (Iscador M),” Journal of Alternative and Complementary Medicine, vol. 13, no. 4, pp. 443–445, 2007. View at Publisher · View at Google Scholar · View at PubMed
  17. I. D. Nagtegaal, C. A. Marijnen, E. K. Kranenbarg et al., “Local and distant recurrences in rectal cancer patients are predicted by the nonspecific immune response; specific immune response has only a systemic effect. A histopathological and immunohistochemical study,” BMC Cancer, vol. 1, pp. 7–16, 2001. View at Google Scholar
  18. F. Garrido, T. Cabrera, A. Concha, S. Glew, F. Ruiz-Cabello, and P. L. Stern, “Natural history of HLA expression during tumour development,” Immunology Today, vol. 14, no. 10, pp. 491–499, 1993. View at Publisher · View at Google Scholar
  19. D. Baskic, L. Acimovic, G. Samardzic, N. L. Vujanovic, and N. N. Arsenijevic, “Blood monocytes and tumor-associated macrophages in human cancer: differences in activation levels,” Neoplasma, vol. 48, no. 3, pp. 169–174, 2001. View at Google Scholar
  20. S. Ostrand-Rosenberg and P. Sinha, “Myeloid-derived suppressor cells: linking inflammation and cancer,” Journal of Immunology, vol. 182, no. 8, pp. 4499–4506, 2009. View at Publisher · View at Google Scholar · View at PubMed
  21. A. Mantovani, “Inflammation and cancer: the macrophage connection,” Medicina, vol. 67, no. 2, pp. 32–34, 2007. View at Google Scholar
  22. C. Sanchez-Torres, G. S. Garcia-Romo, M. A. Cornejo-Cortes, A. Rivas-Carvalho, and G. Sanchez-Schmitz, “CD16+ and CD16- human blood monocyte subsets differentiate in vitro to dendritic cells with different abilities to stimulate CD4+ T cells,” International Immunology, vol. 13, no. 12, pp. 1571–1581, 2001. View at Google Scholar
  23. K. Hostanska, T. Hajto, G. C. Spagnoli, J. Fischer, H. Lentzen, and R. Herrman, “A plant lectin derived from Viscum album induces cytokine gene expression and protein production in cultures of human peripheral blood mononuclear cells,” Natural Immunity, vol. 14, no. 5-6, pp. 295–304, 1995. View at Google Scholar
  24. J. S. Murray, “How the MHC selects Th1/Th2 immunity,” Immunology Today, vol. 19, no. 4, pp. 157–163, 1998. View at Publisher · View at Google Scholar
  25. M. Terabe and J. A. Berzofsky, “Chapter 8 The Role of NKT Cells in Tumor Immunity,” Advances in Cancer Research, vol. 101, pp. 277–348, 2008. View at Publisher · View at Google Scholar
  26. R. Lotfi, H. Schrezenmeier, and M. T. Lotze, “Immunotherapy for cancer: promoting innate immunity,” Frontiers in Bioscience : A Journal and Virtual Library, vol. 14, pp. 818–832, 2009. View at Google Scholar
  27. T. Hajto, K. Hostanska, J. Fischer, and H. Lentzen, “Investigations of cellular parameters to establish the response of a biomodulator: galactoside-specific Lectin from Viscum album plant extract,” Phytomedicine, vol. 3, no. 2, pp. 129–137, 1996. View at Google Scholar
  28. D. Chaudhuri, R. Suriano, A. Mittelman, and R. K. Tiwari, “Targeting the immune system in cancer,” Current Pharmaceutical Biotechnology, vol. 10, no. 2, pp. 166–184, 2009. View at Publisher · View at Google Scholar
  29. L. Ciszak, A. Kosmaczewska, B. Werynska, A. Szteblich, R. Jankowska, and I. Frydecka, “Impaired ζ chain expression and IFN-γ production in peripheral blood T and NK cells of patients with advanced lung cancer,” Oncology Reports, vol. 21, no. 1, pp. 173–184, 2009. View at Publisher · View at Google Scholar
  30. J. Tabiasco, F. Pont, J.-J. Fournié, and A. Vercellone, “Mistletoe viscotoxins increase natural killer cell-mediated cytotoxicity,” European Journal of Biochemistry, vol. 269, no. 10, pp. 2591–2600, 2002. View at Publisher · View at Google Scholar
  31. G Kuttan and R Kuttan, “Immunomodulatory activity of a peptide isolated from Viscum album extract (NSC 635089),” Immunological Investigations, vol. 21, pp. 285–296, 1992. View at Google Scholar
  32. G. M. Stein, U. Edlund, U. Pfüller, A. Büssing, and M. Schietzel, “Influence of polysaccharides from Viscum album L. on human lymphocytes, monocytes and granulocytes in vitro,” Anticancer Research, vol. 19, pp. 3907–3914, 1999. View at Google Scholar
  33. S. Fischer, A. Scheffler, and D. Kabelitz, “Oligoclonal in vitro response of CD4 T cells to vesicles of mistletoe extracts in mistletoe-treated cancer patients,” Cancer Immunology Immunotherapy, vol. 44, no. 3, pp. 150–156, 1997. View at Publisher · View at Google Scholar
  34. H. Franz, A. Kindt, R. Eifler, P. Ziska, R. Benndorf, and I. Junghahn, “Differences in toxicity and antigenicity between mistletoe lectin I and viscotoxin A 3,” Biomedica Biochimica Acta, vol. 42, no. 5, pp. K21–K25, 1983. View at Google Scholar
  35. K. Urech, J. M. Scher, K. Hostanska, and H. Becker, “Apoptosis inducing activity of viscin, a lipophilic extract from Viscum album L,” Journal of Pharmacy and Pharmacology, vol. 57, pp. 101–109, 2005. View at Google Scholar
  36. T. Hajtò, K. Fodor, I. Aponyi, Z. S. Pallai, P. Balogh, P. Németh et al., “Binding of mistletoe lectins from plant extracts to immobilized lactose and N-acetylgalactosamine,” Analytical Chemistry Insights, vol. 2, pp. 43–50, 2007. View at Google Scholar
  37. J. Eck, M. Langer, B. Möckel, K. Witthon, H. Zinke, and H. Lentzen, “Characterisation of recombinant and plant derived mistletoe lectin and their B-chains,” European Journal of Biochemistry, vol. 265, pp. 788–797, 1999. View at Google Scholar
  38. I. B. Pevzner, I. I. Agapov, H. Niwa, N. V. Maluchenko, M. M. Moisenovich, U. Pfüller et al., “Differences in amino acid sequences of mistletoe lectin I and III B-subunits determining carbohydrate binding specificity,” Biochimica et Biophysica Acta, vol. 1675, pp. 155–164, 2004. View at Google Scholar
  39. M. H. Soler, S. Stoeva, C. Schwamborn, S. Wilhelm, T. Stiefel, and W. Voelter, “Complete amino acid sequence of the A chain of mistletoe lectin I,” FEBS Letters, vol. 399, no. 1-2, pp. 153–157, 1996. View at Publisher · View at Google Scholar
  40. M. H. Soler, S. Stoeva, and W. Voelter, “Complete amino acid sequence of the B-chain of mistletoe lectin I,” Biochemical and Biophysical Research Communications, vol. 246, pp. 596–601, 1998. View at Google Scholar
  41. R. Samtleben, H. Wagner, I. Herrmann, and M. Kiefer, “Die Isolektinmuster der Mistel. Eine unüberwindliche Barriere bei der Standardisierung von Mistelprä paraten?” in Die Mistel in der Tumortherapie, R. Scheer, H. Bauer, A. P. Berg, and V. Fintelmann, Eds., pp. 35–39, Grundlagenforschung und Klinik. KVC, Essen, Germany, 2001. View at Google Scholar
  42. J. Müthing, M. Burg, B. Möckel, M. Langer, W. Metelmann-Strupat, and A. Werner, “Preferential binding of the anticancer drug rViscumin (recombinant mistletoe lectin) to terminally α2-6-sialylated neolacto-series gangliosides,” Glycobiology, vol. 12, pp. 485–497, 2002. View at Google Scholar
  43. J Müthing, I Meisen, P Bulau, M Langer, K Witthohn, H Lentzen et al., “Mistletoe lectin I is a sialic acid-specific lectin with strict preference to gangliosides and glycoproteins with terminal Neu5Ac alpha 2-6Gal beta 1-4GlcNAc residues,” Biochemistry, vol. 43, pp. 2996–3007, 2004. View at Google Scholar
  44. I. Kawashima, Y. Yoshida, C. Taya et al., “Expansion of natural killer cells in mice transgenic for IgM antibody to ganglioside GD2: demonstration of prolonged survival after challenge with syngeneic tumor cells,” International Journal of Oncology, vol. 23, no. 2, pp. 381–388, 2003. View at Google Scholar
  45. P. J. Mansky, “Mistletoe and cancer: controversies and perspectives,” Seminars in Oncology, vol. 29, no. 6, pp. 589–594, 2002. View at Publisher · View at Google Scholar · View at PubMed
  46. E. Ernst, “A primer of complementary and alternative medicine commonly used by cancer patients,” The Medical Journal of Australia, vol. 174, pp. 88–92, 2001. View at Google Scholar
  47. L. Simon, D. Prebay, A. Beretz et al., “Complementary and alternative medicines taken by cancer patients,” Bulletin du Cancer, vol. 94, no. 5, pp. 483–488, 2007. View at Publisher · View at Google Scholar