In vitro and in vivo suppression of growth of hepatocellular carcinoma cells by albendazole

Tubulin protein is a major target of drug molecules, and consequently, tubu lin inhibitors have attracted great attention as antimitotic antitumor agen ts for chemotherapeutic use. It has been shown that, the benzimidazole carb amate group of antiparasitics including albendazole act by inhibiting tubul in polymerization. In this study, albendazole was tested in culture against a range of human, rat and mice hepatocellular carcinoma (HCC) cells and in vivo against human SKHEP-1 tumor growth in nude mice. Albendazole induced a dose-dependent inhibition of [H-3]thymidine incorporation in all cell lin es examined and a dramatic decline in cell numbers in SKHEP-1 cells. The in hibitory effect of albendazole was evident at the 100 nM concentration and at 1000 nM, proliferation in all cell lines examined was inhibited by more than 80%, while, proliferation of HepG2, Hep3B and SKHEP-1 were suppressed by more than 90%, compared to control. Cell cycle analysis revealed that, d epending on the dose employed, albendazole can arrest SKHEP-1 cells at both G0-G1 (250 nM) and G2-M (1000 nM) phases of the cycle. Albendazole treatme nt (300 mg/kg per day oral for 20 days) of nude mice inoculated subcutaneou sly with SKHEP-1, led to profound suppression of tumor growth. Immunohistoc hemical analysis of these tumors revealed that compared to control, those t reated with albendazole have lower growth fractions. These findings demonst rate that albendazole strongly suppresses both in vitro and in vivo prolife ration of HCC cells. (C) 2001 Elsevier Science Ireland Ltd. All rights rese rved.