New Wnt/β‐Catenin Signaling Inhibitors Isolated from Eleutherine palmifolia

Catenin tales : Fifteen naphthalene derivatives, including four new glucosides, eleutherinosides B–E, were obtained. Ten of these compounds inhibited transcription of TCF/β‐catenin in STF/293 cells. Compounds 2 and 9 inhibited the transcription of TCF/β‐catenin dose‐dependently and showed selective cytotoxicity against three colorectal cancer cell lines. The decrease of nuclear β‐catenin protein upon treatment of 9 resulted in its inhibitory effect in Wnt signaling.Aberrant Wnt/β‐catenin signaling has recently been implicated in tumorigenesis. On the basis of our screening program targeting inhibition of TCF/β‐catenin transcriptional activity, a plant extract of Eleutherine palmifolia was selected as a hit sample. Activity‐guided fractionations led to the isolation of 15 naphthalene derivatives ( 1 – 15 ), including 4 new glucosides, eleutherinosides B–E ( 1 – 4 ), and 10 of the 15 compounds showed strong activities with high viability among 293T cells. Our data showed that 2 and 9 inhibited the transcription of TCF/β‐catenin in SW480 colon cancer cells in a dose‐dependent manner. These two compounds also showed selective cytotoxicity against three colorectal cancer cell lines. In addition, treatment with 9 led to a significant decrease in the level of nuclear β‐catenin protein, suggesting this reduction to have resulted in the inhibitory effect of 9 on the transcription of TCF/β‐catenin.