Document Type

Article

Publication Date

9-1-2017

Abstract

Glioblastoma is the most common and lethal malignant primary brain tumor for which the development of efficacious chemotherapeutic agents remains an urgent need. The anti-helminthic drug niclosamide, which has long been in use to treat tapeworm infections, has recently attracted renewed interest due to its apparent anticancer effects in a variety of in vitro and in vivo cancer models. However, the mechanism(s) of action remains to be elucidated. In the present study, we found that niclosamide induced cell toxicity in human glioblastoma cells corresponding with increased protein ubiquitination, ER stress and autophagy. In addition, niclosamide treatment led to down-regulation of Wnt/β-catenin, PI3K/AKT, MAPK/ERK, and STAT3 pro-survival signal transduction pathways to further reduce U-87 MG cell viability. Taken together, these results provide new insights into the glioblastoma suppressive capabilities of niclosamide, showing that niclosamide can target multiple major cell signaling pathways simultaneously to effectively promote cell death in U-87 MG cells. Niclosamide constitutes a new prospect for a therapeutic treatment against human glioblastoma.

Comments

© 2017 the authors. Published under Creative Commons Attribution License 4.0. Original published version available at http://doi.org/10.1371/journal.pone.0184324.

Cheng, B., Morales, L., Zhang, R., et al. Niclosamide Induces Protein Ubiquitination and Inhibits Multiple Pro-Survival Signaling Pathways in the Human Glioblastoma U-87 MG Cell Line. PLoS ONE 2017, vol. 12, article no. e0184324.

Publication Title

PLoS ONE

DOI

10.1371/journal.pone.0184324

Included in

Chemistry Commons

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.