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New Wnt/β‐Catenin Signaling Inhibitors Isolated from Eleutherine palmifolia
Author(s) -
Li Xiaofan,
Ohtsuki Takashi,
Koyano Takashi,
Kowithayakorn Thaworn,
Ishibashi Masami
Publication year - 2009
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200800354
Subject(s) - wnt signaling pathway , catenin , beta catenin , carcinogenesis , cytotoxicity , transcription factor , viability assay , transcription (linguistics) , chemistry , cell culture , colorectal cancer , transcriptional activity , biology , signal transduction , cancer research , microbiology and biotechnology , cell , biochemistry , cancer , in vitro , genetics , gene , linguistics , philosophy
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.