Comparison of the effects of Viscum album lectin ML-1 and fresh plant extract (Isorel) on the cell growth in vitro and tumorigenicity of melanoma B16F10.

Numerous findings indicate that specific plant lectins acting against cancer could be major active components of Viscum album extracts, although activity of low molecular weight components (peptides, carbohydrates and alkaloids) might be as essential for the beneficial activity of the plain plant extracts, too. Thus, active principle of Viscum album extracts is still not understood, and is difficult to be analysed because of the complex composition of the extracts and uncertainty of the standardised effectiveness (batch consistency) of the extracts. The aims of this study were to compare the concentration dependent effects of the pure mistletoe lectin (ML-1) with the fresh plant Viscum album extract (Isorel) and its different MW components on the in vitro growth of ConA stimulated lymphocytes, on the growth and tumorigenicity (artificial lung metastases development) of murine melanoma B16F10 cells, and to compare concentration dependent effects of the different types of the Viscum album extracts in vitro (applying novel type of MTT assay). The results obtained indicate that the effects of Isorel used at high dose could be result of toxic activity of the mistletoe lectins ("ML-1 like" activity). Unlike ML-1, if used at low concentrations, Isorel selectively inhibited tumor cells, due the activity of the low MW components. On the other hand, the number of tumor nodules was reduced (in comparison to the control) equally in the lungs of mice injected with B16F10 cells pre-treated in vitro with the plain Viscum album extract or any of its modifications or ML-1. Hence, it is supposed that the beneficial therapeutic effects of Isorel might result from the combined biological activity of the high and the low MW components not lectins only. Similarly, in MTT assay low concentrations of all types of the Viscum album extract showed stronger inhibiting activity for B16F10 and HeLa cells than pure ML-1. According to these results we propose a standardisation of aqueous Viscum album extracts by comparing their and ML-1 concentration dependent activity on the tumor cells in vitro applying MTT bioassay described which should be relevant for further evaluation of their active principle and for improvement of biotherapy of cancer.

The Viscum album preparation Isorel inhibits the growth of melanoma B16F10 by influencing the tumour-host relationship.

The aim of this study was to analyse whether Viscum album (mistletoe; Isorel) modulates the tumour-host relationship and whether this might be a basic mechanism of the antitumorous activity of the drug. The effects of a single intraperitoneal injection of the drug (100 mg/kg single 'planta tota' dose) were analysed for mice-bearing melanoma B16F10 growing in the hind limb. Injection of Isorel reduced the size of the tumour and caused abundant tumour necrosis with inflammatory response, oedema and destruction of the malignant tissue. Furthermore, the lymphocytes of saline-treated tumorous mice were not able to respond to the mitogenic lectin concanavalin A in vitro, while those of mistletoe extract-treated mice showed high reactivity too the mitogen, but only if cultured in the medium supplemented with the plasma of the mistletoe extract-treated mice. Moreover, melanoma cells exposed to the mistletoe extract were more sensitive to the cytotoxic activity of the lymphocytes than the control tumour cells, particularly in the presence of the plasma of mistletoe extract-treated mice. The plasma itself, however, did not show any cytotoxic activity. These results indicate that the antitumour activity of the mistletoe drug is due to a modulation of the tumour-host relationship, mediated by direct cytotoxicity of the drug to tumour cells and/or through a potentiation of immune response by certain, as yet unidentified, growth modifying humoral factors of the host.

Viscum album L. preparation Isorel modifies the immune response in normal and in tumour-bearing mice.

The Viscum album (mistletoe) preparation Isorel is able to destroy tumour cells and to modify immune reactivity against a particular antigen in normal and in tumour-bearing animals. CBA/HZgr mice and methylcholanthrene-induced fibrosarcoma were used in these studies. A single dose of Isorel M (140 mg/kg or 1400 mg/kg body weight) significantly increased the number of plaque forming cells if applied at the time of injection of sheep red blood cells or 1 day earlier. The application of Isorel 1 day after sheep red blood cells did not modify the number of plaque forming cells in comparison to the controls. The higher the dose of Isorel the stronger is the immune response to sheep red blood cells. Furthermore, one dose of Isorel (140 mg/kg body weight) restored the suppressed immune response of fibrosarcoma-bearing mice to a significant extent. Besides modification of the humoral immune response, the survival time of C57BI/GoZgr male skin grafts on syngeneic female recipients was significantly shorter if Isorel was applied at a particular time after grafting. However, according to plaque forming cell numbers, a prolonged application of Isorel was significantly immunosuppressive in normal mice and particularly in tumour-bearing mice. It should be mentioned that the doses of Isorel used in this experiment were much higher than generally used in cancer patients. In view of the immunomodulating effects of Isorel, the monitoring of the immune response of the patients treated with mistletoe preparations is to be recommended.