A New Triterpenoid Saponin from Albizia zygia Induced Apoptosis by Reduction of Mitochondrial Potential Status in Malignant Melanoma Cells

In our ongoing research program on the proapoptotic function of saponins, two previously undescribed saponins, named zygiaosides E ( 1 ) and F ( 2 ), were isolated from the leaves of Albizia zygia . Their structures were established based on extensive analysis of 1D and 2D NMR data, HR-ESI-MS analysis, and by chemical degradation. The proapoptotic effect of zygiaoside E ( 1 ) was evaluated on human malignant melanoma (A375), human epidermoid cancer (A431), and normal Homo sapiens skin tissue (TE 353.SK.) cell lines by cytometric analysis. Zygiaoside E ( 1 ) induced apoptosis of the two human cancer cell lines (A375 and A431) in a dose-dependent manner at 1 mu M but did not induce apoptosis in noncancerous skin cells (TE 353.Sk), even when treated with concentrations up to 15 mu M. The underlying mechanism of the apoptosis induction activity of zygiaoside E ( 1 ) on the mitochondrial membrane potential status in A375 cells was further assessed by monitoring the uptake rate of DiOC6, a mitochondrial specific and voltage-dependent fluorescent dye. The number of malignant melanoma cells emitting high fluorescence levels was decreased when cells were treated with 3 or 5 mu M of zygiaoside E ( 1 ) during either 12 or 24 h, thereby revealing a drop of mitochondrial membrane potential in A375 cells upon treatment, which indicated mitochondrial perturbation.