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Laboratory / Animal / Preclinical Studies

    The immune-system -stimulating and cytotoxic properties of mistletoe have been investigated in laboratory and animal studies.

    Viscotoxins and lectins have been investigated as active components in mistletoe; however, most research has focused on the lectins.[1,2,3,4,5,6,7] Reviewed in [8,9] Purified mistletoe lectins have demonstrated cytotoxic and immune-system-stimulating activities. To date, four different lectins: ML-1, ML-2, ML-3, and Viscum albumchitin -binding agglutinin have been identified in mistletoe extracts. ML-1 (or viscumin) may be responsible for many of mistletoe's biological effects. When a laboratory method was used to selectively deplete ML-1 from Viscum album extracts, their cytotoxic and immune-system-stimulating properties were markedly reduced.[10,11] It should be noted that fermentation eliminates most of the ML-1 in mistletoe extracts.[12] Reviewed in [13,14] Polysaccharide and oligosaccharide components of mistletoe extracts with substantial immune-stimulating properties have been reviewed.[15,16]

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    The molecular structure of ML-1 consists of an alpha chain and a beta chain, which can be separated from one another.[1,17,18] Reviewed in [1,6,7,8,9,13] Each chain type appears to mediate a subset of the activities described for the intact lectin. Cytotoxicity is associated mainly with the alpha chain. In laboratory studies, the ML-1 alpha chain has been coupled to monoclonal antibodies to produce immunotoxins that target and kill specific cell types.[19,20] Reviewed in [21]

    Recombinant ML-1, rML (also known as rViscunim or aviscumin) appears to have the same efficacy as plant-based ML-1 in laboratory studies.[22] Since this is not an extract of mistletoe, it is out of the purview of this summary.

    The beta chain of ML-1 is responsible for binding to the surface of a target cell.[23] Studies of mistletoe lectin binding to cancer cells have examined whether the extent of cell binding can predict disease outcome or survival. Studies show that the prognostic value of ML-1 binding depends on the type of cancer.[24] For human breast cancer cells, the amount of lectin-bound cells correlates positively with disease outcome. However, for human adenocarcinoma of the lung, there is no correlation between the amount of lectin-bound cells and disease survival.[25] Though much research has looked at this particular aspect, there have not been studies that directly link the concentration of that component to any clinical activity of mistletoe.

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