Anti-proliferative effects of diterpenoids fromSagittaria trifoliaL. tubers on colon cancer cells by targeting the NF-kappa B pathway

摘要

A new labdane-type diterpenoid,ent-19-ol-13-epi-manoyl oxide,19-undecane ester, together with ten known diterpenes, were isolated from the ethanolic crude extract of the fresh tubers ofSagittaria trifoliaL. The chemical structures of these compounds were determined by extensive 2-D NMR experiments and by comparison with the data reported in the literature. These compounds showed different inhibitory effects on various human cancer cells. Among these, compound11exhibited potential inhibition effects against human colon cancer cells. Moreover, flow cytometry demonstrated that compound11arrested the cell cycle at the G1 phase and induced cellular apoptosis, accompanied by mitochondrial membrane potential reduction. Mechanistic studies revealed that treatment with compound11inhibited IKK alpha/beta phosphorylation and I kappa B alpha phosphorylation, which subsequently caused the blockage of NF-kappa B p65 phosphorylation and nuclear translocation. Compound11also inhibited the expression of c-Myc, Cyclin D1, and Bcl-2, the downstream targets of NF-kappa B. Therefore, our findings provided insight into the anticancer components ofSagittaria trifoliaL. tubers, which could facilitate their utilization as functional food ingredients.