Modulation of mistletoe (Viscum album L.) lectins cytotoxicity by carbohydrates and serum glycoproteins.
Three D-galactose and/or N-acetyl-D-galactosamine specific mistletoe lectins, ML I, ML II and ML III, were purified by affinity chromatography followed by cation exchange chromatography. These lectins were toxic for Molt 4 cells in culture at concentrations in the pg/ml range, ML III being the most cytotoxic. Carbohydrates able to bind to the B-chain of these lectins inhibited their toxic activity. The digalactosides Gal beta 1,2Gal beta-allyl and Gal beta 1,3Gal beta-allyl were 60 and 30 times, respectively, more potent than D-galactose in their ability to protect the cells from the ML I cytotoxicity. N-acetyl-D-galactosamine and rho-nitrophenyl N-acetylgalactosamine protected mainly from the toxic effects of ML II and III. Protection from cytotoxicity varied in the same order as the affinity of the tested carbohydrates for lectins. Serum glycoproteins particularly haptoglobin, but also alpha 1-acid glycoprotein and transferrin, notably inhibited the cytotoxicity of the lectins. This effect was due to the binding of lectin to the sugar moiety of the glycoprotein because deglycosylated haptoglobin did not have a protective activity on Molt 4 cells. Inhibition of the cytotoxicity of lectins by serum glycoproteins explains why mistletoe extracts containing lectins can be administered to cancer patients without harmful effects.
Frantz
M
M
Laboratoire de Pharmacognosie, Faculté de Pharmacie, Université Louis-Pasteur de Strasbourg, Illkirch, France.
Jung
M L
ML
Ribereau-Gayon
G
G
Anton
R
R
D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000633:toxicity*; D002241:Carbohydrates / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002852:Chromatography, Ion Exchange; D004591:Electrophoresis, Polyacrylamide Gel; D005690:Galactose / Q000494:pharmacology; D005838:Genotype; D006023:Glycoproteins / Q000097:blood / Q000494:pharmacology*; D006242:Haptoglobins / Q000235:genetics; D006801:Humans; D014784:Mistletoe / Q000737:chemistry*; D009961:Orosomucoid / Q000494:pharmacology; D028321:Plant Preparations; D010940:Plant Proteins; D010946:Plants, Medicinal; D054788:Ribosome Inactivating Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000633:toxicity*
D000970:Antineoplastic Agents; D002241:Carbohydrates; D006023:Glycoproteins; D006242:Haptoglobins; D009961:Orosomucoid; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C488862:mistletoe lectin I; C488863:mistletoe lectin II; C488864:mistletoe lectin III; C009674:ribosome inactivating protein, Viscum; D054788:Ribosome Inactivating Proteins; D005690:Galactose