Cancers, Vol. 15, Pages 4619: Repurposing Clemastine to Target Glioblastoma Cell Stemness
Cancers, Vol. 15, Pages 4619: Repurposing Clemastine to Target Glioblastoma Cell Stemness
Cancers doi: 10.3390/cancers15184619
Authors:
Michael A. Sun
Rui Yang
Heng Liu
Wenzhe Wang
Xiao Song
Bo Hu
Nathan Reynolds
Kristen Roso
Lee H. Chen
Paula K. Greer
Stephen T. Keir
Roger E. McLendon
Shi-Yuan Cheng
Darell D. Bigner
David M. Ashley
Christopher J. Pirozzi
Yiping He
Brain tumor-initiating cells (BTICs) and tumor cell plasticity promote glioblastoma (GBM) progression. Here, we demonstrate that clemastine, an over-the-counter drug for treating hay fever and allergy symptoms, effectively attenuated the stemness and suppressed the propagation of primary BTIC cultures bearing PDGFRA amplification. These effects on BTICs were accompanied by altered gene expression profiling indicative of their more differentiated states, resonating with the activity of clemastine in promoting the differentiation of normal oligodendrocyte progenitor cells (OPCs) into mature oligodendrocytes. Functional assays for pharmacological targets of clemastine revealed that the Emopamil Binding Protein (EBP), an enzyme in the cholesterol biosynthesis pathway, is essential for BTIC propagation and a target that mediates the suppressive effects of clemastine. Finally, we showed that a neural stem cell-derived mouse glioma model displaying predominantly proneural features was similarly susceptible to clemastine treatment. Collectively, these results identify pathways essent...
Source: Cancers - Category: Cancer & Oncology Authors: Michael A. Sun Rui Yang Heng Liu Wenzhe Wang Xiao Song Bo Hu Nathan Reynolds Kristen Roso Lee H. Chen Paula K. Greer Stephen T. Keir Roger E. McLendon Shi-Yuan Cheng Darell D. Bigner David M. Ashley Christopher J. Pirozzi Yiping He Tags: Article Source Type: research
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