Potentiation of tumor necrosis factor-alpha-induced apoptosis by mistletoe lectin

Mistletoe lectins (MLs) constitute the active principle in extract preparations from mistletoe, commonly used as immunomodulator in adjuvant tumor therapy. MLs, classified as type II ribosome inactivating proteins, inhibit protein synthesis. Inhibitors of protein synthesis may modify cancer cell response to tumor necrosis factor-alpha (TNF). In the present study, we have hypothesized that the anticancer efficacy of TNF may be potentiated by MLs. In deed, simultaneous treatment of human cervix carcinoma HeLa or breast carcinoma MCF-7 cells with MLs isolated from European or Korean mistletoe rendered them more sensitive to induction of apoptosis by TNF. The mechanism by which MLs amplify the effect of TNF may involve suppression of the survival protein synthesis.