TY - JOUR
T1 - Nonsteroidal anti-inflammatory drugs diclofenac and celecoxib attenuates Wnt/β-Catenin/Tcf signaling pathway in human glioblastoma cells
AU - Sareddy, Gangadhara Reddy
AU - Kesanakurti, Divya
AU - Kirti, Puligurtha Bharadhwaja
AU - Babu, Phanithi Prakash
N1 - Funding Information:
Acknowledgments The authors acknowledge the financial support of CSIR (for providing fellowship to GRS), DBT, ICMR, DST, Government of India, New Delhi.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/11
Y1 - 2013/11
N2 - 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.
AB - 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.
KW - Celecoxib
KW - Diclofenac
KW - Glioblastoma
KW - NSAIDs
KW - Wnt
KW - β-Catenin
UR - http://www.scopus.com/inward/record.url?scp=84885957673&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885957673&partnerID=8YFLogxK
U2 - 10.1007/s11064-013-1142-9
DO - 10.1007/s11064-013-1142-9
M3 - Article
C2 - 24013885
AN - SCOPUS:84885957673
VL - 38
SP - 2313
EP - 2322
JO - Neurochemical Research
JF - Neurochemical Research
SN - 0364-3190
IS - 11
ER -