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Article

Evaluation of β-Catenin Inhibition of Axitinib and Nitazoxanide in Human Monocyte-Derived Dendritic Cells

1
Department of Microbiology, Haukeland University Hospital, Helse Bergen, NO-5021 Bergen, Norway
2
Department of Clinical Science, University of Bergen, NO-5021 Bergen, Norway
3
Broegelmann Research Laboratory, University of Bergen, NO-5021 Bergen, Norway
4
Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Helse Bergen, NO-5021 Bergen, Norway
5
Norway Centre for Cancer Biomarkers, (CCBIO), University of Bergen, NO-5021 Bergen, Norway
*
Authors to whom correspondence should be addressed.
Academic Editors: Carlos Del Fresno Sánchez and Eduardo Lopez-Collazo
Biomedicines 2021, 9(8), 949; https://doi.org/10.3390/biomedicines9080949
Received: 13 July 2021 / Revised: 30 July 2021 / Accepted: 30 July 2021 / Published: 3 August 2021
(This article belongs to the Special Issue Modulation of Innate Immunity in Cancer Immunotherapy)
Modulation of β-catenin signaling has attractive therapeutic potential in cancer immunotherapy. Several studies have found that β-catenin can mediate immune evasion in cancer and promote anti-inflammatory features of antigen-presenting dendritic cells. Many small molecular compounds that inhibit Wnt/β-catenin signaling are currently in clinical development, but none have entered routine clinical use. New inhibitors of β-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 β-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 β-catenin activity, and the effects of axitinib and nitazoxanide were compared with the commercial β-catenin inhibitor ICG-001. Assays, including genome-wide RNA-sequencing, indicated that neither axitinib nor nitazoxanide demonstrated considerable β-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 β-catenin inhibitors in monocyte-derived dendritic cells. View Full-Text
Keywords: monocyte-derived dendritic cell; beta-catenin; ICG-001; axitinib; nitazoxanide monocyte-derived dendritic cell; beta-catenin; ICG-001; axitinib; nitazoxanide
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MDPI and ACS Style

Azeem, W.; Bakke, R.M.; Gabriel, B.; Appel, S.; Øyan, A.M.; Kalland, K.-H. Evaluation of β-Catenin Inhibition of Axitinib and Nitazoxanide in Human Monocyte-Derived Dendritic Cells. Biomedicines 2021, 9, 949. https://doi.org/10.3390/biomedicines9080949

AMA Style

Azeem W, Bakke RM, Gabriel B, Appel S, Øyan AM, Kalland K-H. Evaluation of β-Catenin Inhibition of Axitinib and Nitazoxanide in Human Monocyte-Derived Dendritic Cells. Biomedicines. 2021; 9(8):949. https://doi.org/10.3390/biomedicines9080949

Chicago/Turabian Style

Azeem, Waqas, Ragnhild M. Bakke, Benjamin Gabriel, Silke Appel, Anne M. Øyan, and Karl-Henning Kalland. 2021. "Evaluation of β-Catenin Inhibition of Axitinib and Nitazoxanide in Human Monocyte-Derived Dendritic Cells" Biomedicines 9, no. 8: 949. https://doi.org/10.3390/biomedicines9080949

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