New Wnt/beta-catenin signaling inhibitors isolated from Eleutherine palmifolia.
Aberrant Wnt/beta-catenin signaling has recently been implicated in tumorigenesis. On the basis of our screening program targeting inhibition of TCF/beta-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/beta-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 beta-catenin protein, suggesting this reduction to have resulted in the inhibitory effect of 9 on the transcription of TCF/beta-catenin.
Li
Xiaofan
X
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Ohtsuki
Takashi
T
Koyano
Takashi
T
Kowithayakorn
Thaworn
T
Ishibashi
Masami
M
D045744:Cell Line, Tumor; D006027:Glycosides / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D006801:Humans; D027621:Iridaceae / Q000737:chemistry*; D009281:Naphthalenes / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D010936:Plant Extracts / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D006027:Glycosides; D009281:Naphthalenes; D010936:Plant Extracts; D051153:Wnt Proteins; D051176:beta Catenin