Modulation of Mistletoe (Viscum album L.) Lectins Cytotoxicity by Carbohydrates and Serum Glycoproteins

Abstract

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.

Multiple Active Compounds from Viscum album L. Synergistically Converge to Promote Apoptosis in Ewing Sarcoma

“…Furthermore, Frantz et al . demonstrated, that mistletoe lectins can also bind Serum glycoproteins as haptoglobin, alpha 1-acid glycoprotein and transferrin inhibiting the cytotoxicity of the lectins [62] Although viscumTT had no synergistic effect in vivo , it still demonstrated effectiveness intratumorally and intravenously. To validate the effect of viscumTT in vivo , we injected viscumTT in a patient-derived xenograft model intratumorally and intravenously.…”

A new development of triterpene acid‐containing extracts from Viscum album L. displays synergistic induction of apoptosis in acute lymphoblastic leukaemia

“…For our experiments, we used ML‐I containing aqueous mistletoe extracts from plant material harvested from apple trees, whereas in former investigations, ML‐II/III (Helixor Heilmittel GmbH & Co. KG, Rosenfeld, Germany)‐containing mistletoe extracts harvested from pine and fir trees were used. It is known that ML‐I is significantly less toxic compared to ML‐III (64,65). Moreover, we detected marked difference between extracts concerning tolerance, in vivo .…”

Viscum album neutralizes tumor-induced immunosuppression in a human in vitro cell model

“…Mistletoe lectin was isolated and depleted from VAEI by affinity chromatography with immobilized α1-acid glycoprotein. α1-acid glycoprotein was used because of its high and non-selective affinity for all three isoforms of ML [28]. 50 mg of α1-acid glycoprotein (orosomucoid from Sigma-Aldrich, Buchs, Switzerland) was coupled to 2 ml Affi-gel 15 (Bio-Rad, Cressier, Switzerland) according to the manufacturer’s instructions.…”