MISTLETOE LECTIN SYNERGIZES WITH PACLITAXEL IN HUMAN SK-Hep1 HEPATOCARCINOMA CELLS

Abstract

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 nontoxic 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.

Key Words :

• Mistletoe lectin
• Paclitaxel
• Hepatoma
• Apoptosis