Ginsenoside 20( S)-Protopanaxadiol Suppresses Viability of Human Glioblastoma Cells via Down-regulation of Cell Adhesion Proteins and Cell-cycle Arrest

Background: Pharmacologically active components of ginseng, particularly protopanaxadiol (PPD)-type ginsenosides, have potent anticancer effects, although their effects on highly malignant glioblastoma multiforme (GBM) have not been systemically evaluated. Identification of effective anticancer ginsenosides and further delineation of their mechanisms of action may provide valuable information that aids in the development of alternative or adjuvant therapy for malignant cancer. Materials and Methods: We examined the viability of human GBM U251-MG and U87-MG cells treated with structurally related PPD-type ginsenosides, including F2, Rh-2, compound K (C-K), and PPD. Results: Incubation with PPD, C-K, and Rh-2 significantly reduced the viability of U251-MG and U87-MG cells in a dose-and time-dependent manner. The cytotoxic effect of PPD was accompanied by reduced expression of cell adhesion proteins, including N-cadherin and integrin beta 1, which led to reduced phosphorylation of focal adhesion kinase. Furthermore, incubation with PPD reduced the expression of cyclin D1 and subsequently induced cell-cycle arrest at the G(1) phase. Conclusion: These results collectively indicate that PPD might provide a new strategy for treating malignant GBM, which is quite resistant to conventional anticancer treatment.