Cytotoxic Effects of Triterpenoid Saponins from Androsace umbellata against Multidrug Resistance (MDR) and Non-MDR Cells

Cytotoxicity-guided fractionation and separation of MeOH extract from Androsace umbellata (Lour.) Merr. led to the isolation of four triterpenoid saponins. Compounds isolated from the n-BuOH soluble fraction were identified as saxifragifolin C (1), A (2), B (3), and D (4) by spectroscopic analysis. Antiproliferative effect of isolated compounds were evaluated by the sulfor-hodamin B assay against multidrug resistance (MDR; MES-SA/DX5 and HCT15/CL02) and non-MDR (A549, SK-OV-3, SK-MEL-2, MES-SA, and HCT15) human tumor cell lines. All compounds exhibited strong cytotoxicity against non-MDR human tumor cell lines with 1050 values of 0.19-2.37 mu M. MDR cells and non-MDR cells had similar sensitivity to these compounds, however, MDR cells were highly resistant to doxorubicin. Compounds 1-4 induced an increase in the per centage of Annexin V-binding cells, indicating that 1-4 induced apoptosis in RAW 264.7 cells. Also, the condensation of nuclei, a characteristic morphological change of apoptosis, was observed in RAW 264.7 cells by the treatment with n-BuOH fraction, compounds 3 and 4, respectively.