Ginseng is a well-known herb medicine that has been used for thousands of years. The major medicinal ingredients in ginseng are ginsenosides, a group of triterpene saponins. While a wide range of pharmacological effects of various ginsenosides have been reported, only few ginsenosides (Rh2 and Rg3) have shown cytotoxicity in cancer cells. In the present study, we investigated the anti-tumor activity of an aglycon Rh2 derivative, namely aglycon 20(S)-protopanaxadiol (aPPD). Human tumor cells of various types were treated with aPPD followed by cytotoxicity assay. Aglycon PPD induced tumor apoptotic cell death in a dose-response fashion. Results of Western blotting revealed that all caspases including caspase 3, 8, and 9 were activated 3 hours after treatment. However, aPPD can also induce apoptosis through a pathway independent of above caspases. In addition, aPPD synergistically enhances cytotoxicity of various chemotherapy drugs on cancer cells, especially for the multidrug resistant cancer cells. Further study showed that aPPD significantly blocked p-glycoprotein in a mechanism different from verapamil. In an intracranial rat glioma model, animals were orally given aPPD at doses of 2.5, 12 and 25mg/kg for 5 days. Among animals treated with 12 and 25mg/kg, 40% survived longer than 42 days comparing to the average of 18 days in control animals. Furthermore, more than 50% of survived animals were found completed tumor regression by autopsy. No toxicity was detectable. The above results suggest that aglycon PPD possesses effective anti-tumor activity and therefore is a potential anti-tumor drug candidate.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]