Triterpenoid saponins from Ardisia gigantifolia stapf. and mechanism on inhibiting proliferation of MDA-MB-231 cells.

Seventeen 13, 28-epoxy triterpenoid saponins obtained from Ardisia gigantifolia stapf. were evaluated their anti-proliferative activities on MCF-7 cells. The structure-activity relationship analysis indicated that CH3 group at C-30, four saccharide units with L-rhamnose at R6 in the sugar units are crucial for the cytotoxic activity on MCF-7. Compounds 1, 2, 6, 7, 12, 14 were selected to identify the anti-proliferative activity on the other three breast cancer cell lines (T47D, MDA-MB-231 and SK-BR-3). Compounds (2, 6, 7) with good activity on MCF-7 also showed activity on T47D, MDA-MB-231 and SK-BR-3. Compounds (12 and 14) without cytotoxic activity on MCF-7 almost showed no activities on the other three cell lines. For the triple-negative breast cancer MDA-MB-231，Saponins 7 and 14 showed selective cytotoxic activity, 7 showed much more activity than 14, suggesting the six saccharide units in sugar units and CH3 on C-30 were the key moieties for the anti-proliferative activities. Further molecular mechanism of saponin 7 was studied on inhibiting cell proliferation of MDA-MB-231 cells. Saponin 7 could enhance apoptosis, arrest cell cycles, decrease MMPs, and considered the involvement of ROS may explain this conundrum.