Evaluation Of Beta-Catenin Inhibition Of Axitinib And Nitazoxanide In Human Monocyte-Derived Dendritic Cells

Modulation of beta-catenin signaling has attractive therapeutic potential in cancer immunotherapy. Several studies have found that beta-catenin can mediate immune evasion in cancer and promote anti-inflammatory features of antigen-presenting dendritic cells. Many small molecular compounds that inhibit Wnt/beta-catenin signaling are currently in clinical development, but none have entered routine clinical use. New inhibitors of beta-catenin signaling are consequently desirable. Here, we have tested, in monocyte-derived dendritic cells, the effects of two small molecular compounds, axitinib and nitazoxanide, that previously have been discovered to inhibit beta-catenin signaling in colon cancer cells. Immature and lipopolysaccharide-matured dendritic cells prepared from healthy blood donor buffy coats were stimulated with 6-bromoindirubin-3'-oxime (6-BIO) to boost basal beta-catenin activity, and the effects of axitinib and nitazoxanide were compared with the commercial beta-catenin inhibitor ICG-001. Assays, including genome-wide RNA-sequencing, indicated that neither axitinib nor nitazoxanide demonstrated considerable beta-catenin inhibition. Both compounds were found to be less toxic to monocyte-derived dendritic cells than either 6-BIO or ICG-001. Axitinib stimulated several aspects of dendritic cell function, such as IL12-p70 secretion, and counteracted IL-10 secretion, according to the present study. However, neither axitinib nor nitazoxanide were found to be efficient beta-catenin inhibitors in monocyte-derived dendritic cells.