Potent apoptotic effects of saponins from Liliaceae plants in L1210 cells

We isolated eight saponins, a hexacyclic lanosterol tetraglycoside (1), a 27-norlanosterol tetraglycoside (2) and six spirostanol oligoglycosides (3-8), from the plants of the family Liliaceae. In murine leukaemic L1210 cells, saponins 5 and 7 at a concentration of 1 microM showed potent cytotoxic activity and the activities were in the following decreasing order: 5, 7, 1, 3, 2, 8, 4, 6. At a concentration of 10 microM, not only 5 and 7 but also 3 and 8 markedly caused cell death. The flow cytometric analysis indicated that 7 and 8 caused a concentration- and time-dependent apoptosis of L1210 cells (EC50 value = approximately 5 microM). The morphological observation using a light microscope revealed that both 7 and 8 induced shrinkage in cell soma and chromatin condensation, suggesting apoptotic cell death. Moreover, in agarose gel electrophoretic analysis, a typical apoptotic DNA ladder pattern was observed after treatment with both 7 and 8. These results suggest that 7 and 8 caused the death of L1210 cells through the apoptotic process. These compounds may become powerful pharmacological tools for studying the molecular mechanism of apoptosis.