Nonsteroidal anti-inflammatory drugs diclofenac and celecoxib attenuates Wnt/β-Catenin/Tcf signaling pathway in human glioblastoma cells

Gangadhara Reddy Sareddy, Divya Kesanakurti, Puligurtha Bharadhwaja Kirti, Phanithi Prakash Babu

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Glioblastoma, the most common and aggressive primary brain tumors, carry a bleak prognosis and often recur even after standard treatment modalities. Emerging evidence suggests that deregulation of the Wnt/β-catenin/Tcf signaling pathway contributes to glioblastoma progression. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit tumor cell proliferation by suppressing Wnt/β-catenin/Tcf signaling in various human malignancies. In this study, we sought to inhibit Wnt/β-catenin/Tcf signaling in glioblastoma cells by the NSAIDs diclofenac and celecoxib. Both diclofenac and celecoxib significantly reduced the proliferation, colony formation and migration of human glioblastoma cells. Diclofenac and celecoxib downregulated β-catenin/Tcf reporter activity. Western and qRT-PCR analysis showed that diclofenac and celecoxib reduced the expression of β-catenin target genes Axin2, cyclin D1 and c-Myc. In addition, the cytoplasmic accumulation and nuclear translocation of β-catenin was significantly reduced following diclofenac and celecoxib treatment. Furthermore, diclofenac and celecoxib significantly increased phosphorylation of β-catenin and reduced the phosphorylation of GSK3β. These results clearly indicated that diclofenac and celecoxib are potential therapeutic agents against glioblastoma cells that act by suppressing the activation of Wnt/β-catenin/Tcf signaling.

Original languageEnglish (US)
Pages (from-to)2313-2322
Number of pages10
JournalNeurochemical Research
Volume38
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • Celecoxib
  • Diclofenac
  • Glioblastoma
  • NSAIDs
  • Wnt
  • β-Catenin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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