BASI, a potent small molecular inhibitor, inhibits glioblastoma progression by targeting microrna-mediated β-catenin signaling

Abstract

Background and Aims: The nuclear localization of β-catenin, a mediator of canonical Wnt signaling, has been indicated in a variety of cancers and is frequently related to tumor progression and metastasis. Therefore, targeting β-catenin is an attractive therapeutic strategy for cancers. Methods: Herein, we identified a natural, small molecule inhibitor of β-catenin signaling, BASI, and evaluated its therapeutic efficacy both in vitro and in orthotopic mouse models of glioma. Results: BASI significantly suppressed proliferation and invasion and induced apoptosis in glioblastoma cells and resulted in the remarkable attenuation of orthotopic tumor growth in vivo. Furthermore, we found that BASI altered the expression of several microRNAs, which mediated the posttranscriptional silencing of β-catenin expression either directly or indirectly through a von Hippel-Lindau (VHL)-mediated β-catenin degradation pattern. Conclusions: Taken together, our findings offer preclinical validation of BASI as a promising new type of β-catenin inhibitor with a mechanism of inhibition that has broad potential for the improved treatment of glioblastoma. © 2014 John Wiley & Sons Ltd.