Induction of apoptosis in human lymphocytes treated with VISCUM ALBUM L. is mediated by the mistletoe lectins

Journal/Book: Cancer Letters 99, 59-72. 1996;

Abstract: Viscum album L. (VAL) is a phytopreparation used in adjuvant cancertherapy with both immunostimulatory and DNA stabilizing properties atlow drug concentrations and cytostatic/cytotoxic properties at higherconcentrations. The present work examines the cytotoxic effects of VALextracts produced from mistletoes grown on different host trees and ofpurified toxic proteins from VAL, such as the D-galactose-specificlectin I (ML I), the N-acetyl-D-galactosamine-specific ML II and ML III,and crude viscotoxins towards cultured human lymphocytes. The decreasein the number of cultured lymphocytes and blast cells treated with wholeplant extracts from VAL was host tree-specific. Nevertheless, there wasno close correlation to the content of MLs or viscotoxins. Using thepurified proteins, it became obvious that the cell killing was mediatedby the induction of apoptosis, as measured by the appearance of ahypodiploid DNA peak using flow cytometry. ML III was the most effectiveto induce apoptosis, followed by ML II and ML I, while the viscotoxinsand oligosaccharides from VAL did not. By measuring the surfaceexpression of IL-2R alpha chains, transferrin receptors and APO-1/Fasmolecules on non-apoptotic T cells, no significant changes were observedat low ML concentrations (1 ng/ml), but their decrease at higher ones.Our findings suggest that there might be at least two different ways ofcell killing operative in VAL-mediated cytotoxicity: (a) the typicalapoptotic cell death with the appearance of hypo-diploid nuclei, and (b)a direct or indirect killing by damaging the cell membrane withsubsequent influx of Ca2+ and of the DNA intercalating dye propidiumiodide and cell shrinkage. These effects might not be exclusive, as theyprobably occur simultaneously. Author.

Keyword(s): APOPTOSIS/ DE (drug effects)

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