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.
Doser
C
C
Institute of Genetics, University of Hohenheim, Stuttgart, Fed. Rep. of Germany.
Doser
M
M
Hülsen
H
H
Mechelke
F
F
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