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 PMID:33341676  

A novel dipeptide type inhibitor of the Wnt/β-catenin pathway suppresses proliferation of acute myelogenous leukemia cells.

Ryosuke Wakabayashi | Yasunao Hattori | Shigekuni Hosogi | Yuki Toda | Kazuyuki Takata | Eishi Ashihara
Biochemical and biophysical research communications | 2021

The Wnt/β-catenin pathway is an attractive target for the treatment of acute myelogenous leukemia (AML), since aberrant activation of the Wnt/β-catenin pathway contributes to carcinogenesis in various types of cancers including AML. Screening of an in-house compound library, constructed at Kyoto Pharmaceutical University, identified a novel compound designated "31" that was found to be an inhibitor of the Wnt/β-catenin pathway. The compound inhibited T-cell factor (TCF) activity in a TCF firefly luciferase-reporter assay and suppressed the proliferation of several human AML cell lines in a dose-dependent manner. Compound 31 arrested the cell cycle of AML cells at the G1 stage and induced apoptosis. Decrease in protein and mRNA expression level of Wnt pathway-related molecules was confirmed by the analyses of western blotting and quantitative reverse transcription-polymerase chain reaction. In addition, compound 31 combined with idarubicin synergistically inhibited the proliferation of AML cells. In conclusion, these results strongly suggest that compound 31 has potential as a novel anti-AML agent targeting the Wnt/β-catenin signaling pathway.

Pubmed ID: 33341676

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