Niclosamide induces protein ubiquitination and inhibits multiple pro-survival signaling pathways in the human glioblastoma U-87 MG cell line

Benxu Cheng, Liza Doreen Morales, Yonghong Zhang, Shizue Mito, Andrew Tsin

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0184324
JournalPLoS One
Volume12
Issue number9
DOIs
StatePublished - Sep 1 2017
Externally publishedYes

Fingerprint

Niclosamide
niclosamide
Ubiquitination
Glioblastoma
Cells
cell lines
Cell Line
Survival
Proteins
proteins
Cestode Infections
Cell signaling
Catenins
Signal transduction
neoplasms
tapeworms
autophagy
Autophagy
phosphatidylinositol 3-kinase
Cell death

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Niclosamide induces protein ubiquitination and inhibits multiple pro-survival signaling pathways in the human glioblastoma U-87 MG cell line. / Cheng, Benxu; Morales, Liza Doreen; Zhang, Yonghong; Mito, Shizue; Tsin, Andrew.

In: PLoS One, Vol. 12, No. 9, e0184324, 01.09.2017.

Research output: Contribution to journalArticle

Cheng, Benxu ; Morales, Liza Doreen ; Zhang, Yonghong ; Mito, Shizue ; Tsin, Andrew. / Niclosamide induces protein ubiquitination and inhibits multiple pro-survival signaling pathways in the human glioblastoma U-87 MG cell line. In: PLoS One. 2017 ; Vol. 12, No. 9.
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