Apoptosis pathway of triterpenoids from Tiarella polyphylla on HL-60 cells

Triterpenoid saponins including tiarellic acid and randianin were isolated from Tiarella polyphylla in our previous work. In the present study, we focused on apoptosis pathway of tiarellic acid and randianin on clone 15 HL-60 human promyelocytic leukemic cells which have eosinophilic character. Both tiarellic acid and randianin exhibited the caspase-3 activation, induction of DNA fragmentation, and elevation of annexin V stained cells showing cytoplasmic membrane flipping typically detected in early apoptotic cells. Following experiments showed that Bcl-2 was down-regulated and Bax expression and cytochrome C release was promoted by both compounds, which mean these compounds seem to be involved in mitochondrial pathway. Dot blot analysis using an apoptosis expression array showed that TRAF-1, TRAF-2 and IL-4R were up-regulated by tiarellic acid, but no significantly modulated genes were found in the randianin-treated cells. These results suggest that both tiarellic acid and randianin is able to induce apoptosis of clone 15 HL-60 cells via caspase-3- and mitochondria-mediated pathway, even though some apoptosis-related genes are modulated differently by two compounds.