Influence of carbohydrates on the cytotoxicity of an aqueous mistletoe drug and of purified mistletoe lectins tested on human T-leukemia cells.
Partially and highly purified lectins from Viscum album L. (mistletoe) cause a dose-dependent decrease of viability of human leukemia cell cultures, MOLT-4, after 72 h treatment. The LC50 of the partially purified 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 protein concentration of an aqueous mistletoe drug was required to obtain similar cytotoxic effects on MOLT-4 cells. Cytotoxicity of the highly purified lectin was preferentially inhibited by D-galactose and lactose, cytotoxicity of the mistletoe drug and the partially purified lectin were preferentially inhibited by lactose and N-acetyl-D-galactosamine (GalNAc). Two lectin fractions with almost the same cytotoxic activity on MOLT-4 cells but with different carbohydrate affinities were isolated by affinity chromatography from the mistletoe drug: mistletoe lectin I with an affinity to D-galactose and GalNAc and mistletoe lectin II with an affinity to GalNAc. The lectin fractions and the mistletoe drug inhibited protein synthesis of MOLT-4 cells stronger than DNA synthesis. Furthermore a subpopulation of MOLT-4, resistant to cytotoxic doses of both the mistletoe drug and the mistletoe lectins, was shown to exhibit a reduced amount of GalNAc and N-acetyl-D-glucosamine in their cellular glycoproteins which are probably responsible for the binding of the cytotoxic lectins. These results indicate that lectins are the main toxins in the mistletoe drug.
Institute of Genetics, University of Hohenheim, Stuttgart, Fed. Rep. of Germany.
C
C
Doser
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M
Doser
H
H
Hülsen
F
F
Mechelke
D002241:Carbohydrates / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D002849:Chromatography, Gas; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D037102:Lectins / Q000494:pharmacology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology*; D014784:Mistletoe / Q000032:analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010936:Plant Extracts / Q000494:pharmacology*; D037121:Plant Lectins; D010946:Plants, Medicinal; D010947:Plants, Toxic; D012278:Ricinus / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
D002241:Carbohydrates; D004273:DNA, Neoplasm; D006023:Glycoproteins; D037102:Lectins; D009363:Neoplasm Proteins; D010936:Plant Extracts; D037121:Plant Lectins