Influence of carbohydrates on the cytotoxicity of an aqueous mistletoe drug and of purified mistletoe lectins tested on human T-leukemia cells

Journal/Book: Arzneim. Forsch./Drug Res. 39 (6), 647-651. 1989;

Abstract: Partially and highly purified lectins from Viscum album L. (mistletoe)cause a dose-dependent decrease of viability of human leukemia cellcultures, MOLT-4, after 72 h treatment. The LC50 of the partiallypurified lectin was 27.8 ng/ml, of the highly purified lectin 1.3 ng/ml.Compared to the highly purified lectin a 140-fold higher proteinconcentration of an aqueous mistletoe drug was required to obtainsimilar cytotoxic effects on MOLT-4 cells. Cytotoxicity of the highlypurified lectin was preferentially inhibited by D-galactose and lactose,cytotoxicity of the mistletoe drug and the partially purified lectinwere preferentially inhibited by lactose and N-acetyl-D-galactosamine(GalNAc). Two lectin fractions with almost the same cytotoxic activityon MOLT-4 cells but with different carbohydrate affinities were isolatedby affinity chromatography from the mistletoe drug: mistletoe lectin Iwith an affinity to D-galactose and GalNAc and mistletoe lectin II withan affinity to GalNAc. The lectin fractions and the mistletoe druginhibited protein synthesis of MOLT-4 cells stronger than DNA synthesis.Furthermore a subpopulation of MOLT-4, resistant to cytotoxic doses ofboth the mistletoe drug and the mistletoe lectins, was shown to exhibita reduced amount of GalNAc and N-acetyl-D-glucosamine in their cellularglycoproteins which are probably responsible for the binding of thecytotoxic lectins. These results indicate that lectins are the maintoxins in the mistletoe drug. Author.

Keyword(s): CARBOHYDRATES/ PD (pharmacology)

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