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Nonsteroidal Anti-inflammatory Drugs Diclofenac and Celecoxib Attenuates Wnt/β-Catenin/Tcf Signaling Pathway in Human Glioblastoma Cells

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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.

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Acknowledgments

The authors acknowledge the financial support of CSIR (for providing fellowship to GRS), DBT, ICMR, DST, Government of India, New Delhi.

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Authors and Affiliations

  1. Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India

    Gangadhara Reddy Sareddy & Phanithi Prakash Babu

  2. Department of Plant Sciences, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India

    Divya Kesanakurti & Puligurtha Bharadhwaja Kirti

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  1. Gangadhara Reddy Sareddy
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  2. Divya Kesanakurti
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Correspondence to Phanithi Prakash Babu.

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Sareddy, G.R., Kesanakurti, D., Kirti, P.B. et al. Nonsteroidal Anti-inflammatory Drugs Diclofenac and Celecoxib Attenuates Wnt/β-Catenin/Tcf Signaling Pathway in Human Glioblastoma Cells. Neurochem Res 38, 2313–2322 (2013). https://doi.org/10.1007/s11064-013-1142-9

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  • DOI: https://doi.org/10.1007/s11064-013-1142-9

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