Biochemical, histochemical and cell biological investigations on the actions of mistletoe lectins I, II and III with human breast cancer cell lines

Abstract

Cytotoxicity of the mistletoe lectins I, II and III towards six human breast cancer cell lines was assessed using the Mossman assay. In addition, binding of the three mistletoe lectins to the separated membrane glycoproteins of these cell lines, the binding and uptake of these lectins into the cells in tissue culture and the binding of the lectins to histological preparations of these cell lines were analysed. The results indicate that there are quantitative differences concerning the toxicity of these three lectins towards the different cell lines. Furthermore, the lectin binding pattern in the cell lines differed. In Western blots, several membrane glycoproteins were labelled by the lectins. Our results indicate subtle differences between the three lectins with regard to the parameters mentioned above; however, the toxicity of all three lectins from mistletoe is so similar that they all seem suitable for the construction of immunotoxins.

In U-937 promonocytes, misteltoe lectin I increases basal [Ca2+]i, enhances histamine H1- and complement C5a-receptor-mediated rises in [Ca2+]i, and induces cell death

“…Because ML I is known to inhibit proliferation and to induce cell death via apoptosis in various cell types (Janssen et al 1993;Schumacher et al 1995;Büssing et al 1996), we studied the effect of the lectin on growth and viability of U-937 cells (Fig. 5).…”

“…As inductor of apoptosis, we selected ML I for the following reasons. First, ML I has already been shown to inhibit growth of lymphocytes and various tumor cell lines and to induce cell death via apoptosis Janssen et al 1993;Schumacher et al 1995;Büssing et al 1996). Second, at concentrations that are slightly lower as, or similar to, the ones leading to apoptosis, ML I induces secretion of cytokines such as interleukin 1 and tumor necrosis factor-a (Hajto et al 1990), suggesting that intercellular signal molecules participate in ML I-triggered apoptosis.…”

Influence of mistletoe lectins and cytokines induced by them on cell proliferation of human melanoma cells in vitro

“…Hence, those melanomas with highest density of ML-I binding sites have the worst prognosis. Binding of the lectin to cell surface receptors and internalisation are the prerequisite for lectin-induced cytotoxic effects (Schumacher et al, 1995a;Schwarz et al, 1999). If binding intensity of the MLs was correlated with their respective cytotoxic effect, this would mean an added benefit for the melanoma patients, as especially those melanomas with a highly metastatic potential would be targeted by ML-I toxicity.…”

Tumor‐associated CD75s gangliosides and CD75s‐bearing glycoproteins with Neu5Acα2‐6Galβ1‐4GlcNAc residues are receptors for the anticancer drug rViscumin

“…In this context, the recently characterized lectin from the fruiting body of the polypore mushroom Polyporus squamosus with strict specificity for α2-6-linked sialic acid (50) renders this lectin a valuable tool for glycobiological studies in biomedical and cancer research. Using ML-I, recently redefined as a sialic acid binding lectin (14), and the closely related mistletoe lectins ML-II and ML-III, subtle different binding patterns in Western blots and in histological preparations of human breast cancer cell lines were observed (51). Thus, distinct binding structures are suggested to be the reason for these differences, and the identification of the oligosaccharide ligands of ML-II and ML-III are a challenge for future investigations.…”