Mistletoe lectin synergizes with paclitaxel in human SK-hep1 hepatocarcinoma cells

The effect of mistletoe lectin I (ML-I), an inhibitor of ribosomal protein synthesis, on the in vitro cytotoxicity of a clinically important anticancer drug, paclitaxel, was studied on cultured human hepatocarcinoma SK-Hep1 cells using the microculture tetrazolium test. The interaction between these two agents was analyzed for true synergism using the ED50 isobologram. Synergism was observed in the simultaneous treatment of the cells with ML-I in combination with paclitaxel. In addition, 24-h exposure of the cells to a non-toxic dose of ML-I and lower toxic doses of paclitaxel in combination resulted in apoptotic cell death, as observed by agarose-gel electrophoresis of low-molecular-weight DNA and DNA flow cytometry. Thus, the results presented here indicate the potential clinical usefulness of ML-I combination therapy with paclitaxel.