Suppression of growth of tumour cell lines in vitro and tumours in vivo by mistletoe lectins

Abstract

A variety of studies have shown that incubation of different tumour cell lines with mistletoe lectins (MLs) in vitro has a marked cytotoxic effect. In the concentration range of low cytotoxicity cell death induced by ML-I is quantitatively due to apoptotic processes. The first events observed being membrane perforation and protusions. Simultaneous treatment of certain tumour cells with MLs rendered them more sensitive to induction of apoptosis by TNFa. The immunomodulatory activity of ML-I was investigated by measuring cytokine release and the results confirmed that cytokine induction by the lectin is regulated at the transcriptional level. ML-I has been shown to potentiate the effect of chemotherapeutic drugs. In addition to an in vitro effect a number of workers have demonstrated that MLs suppress tumour growth in vivo. Mistletoe lectins have been administered to animals locally to the tumour, systemic, subcutaneously or by the oral route via the diet. In many cases apoptosis was observed in the tumour and instances where complete tumour ablation has occurred have been reported. It has been hypothesized that the anticancer efficacy of tumour necrosis factor-alpha (TNFa) is potentiated by MLs isolated from both European and Korean mistletoe. There is accumulating evidence that both types of MLs are able to induce an anti-angiogenic response in the host suggesting that the anti-metastatic effect observed on a series of tumour cell lines in mice is in part due to an inhibition of tumour-induced angiogenesis and in part due to an induction of apoptosis.