Daphnane Diterpenoids from Inhibit PI3K/Akt/mTOR Signaling and Induce Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells

Seven new daphnane-type diterpenoids, daphgenkins A-G (-), and 15 known analogues (-) were isolated from the flower buds of . Their structures and absolute configurations were elucidated by spectroscopic data and calculated ECD analyses. The cytotoxicities of all daphnane-type diterpenoids (-) obtained were evaluated against three human colon cancer cell lines (SW620, RKO, and LoVo). Compounds , , and exhibited cytotoxic effects against the SW620 and RKO cell lines, with IC values in the range of 3.0-9.7 μM. The most active new compound, , with an IC value of 3.0 μM against SW620 cells, was evaluated further for its underlying molecular mechanism. Compound induced G/G cell cycle arrest, leading to the induction of apoptosis in SW620 cells. Also, it induced cancer cell apoptosis by an increased ratio of Bax/Bcl-2, activated cleaved caspase-3 and caspase-9, and upregulated PARP. Finally, compound significantly inhibited PI3K/Akt/mTOR signaling in SW620 cells. Together, the results suggest that compound may be a suitable lead compound for further biological evaluation.