Celecoxib inhibits the expression of survivin via the suppression of promoter activity in human colon cancer cells

Naoko Sakoguchi-Okada, Fumi Takahashi-Yanaga, Kazuhiro Fukada, Fumie Shiraishi, Yoji Taba, Yoshikazu Miwa, Sachio Morimoto, Mitsuo Iida, Toshiyuki Sasaguri

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74 Citations (Scopus)


We investigated the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on human colon cancer cell lines to clarify the mechanisms underlying the chemopreventive effect of NSAIDs. Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, induced apoptosis and strongly reduced the expression of an anti-apoptotic protein, survivin, in both protein and mRNA levels in HCT-116 cells. Subsequently, we conducted luciferase reporter assay using a reporter gene driven by the human survivin promoter. A series of analyses using luciferase reporter constructs containing fragments of the survivin promoter and electrophoretic mobility shift assay indicated that the -75/-66 bp region relative to the initiating codon was involved in celecoxib action to suppress survivin promoter activity. Celecoxib also suppressed the activity of TOPflash, T-cell factor reporter plasmid, and the reporter gene driven by the human cyclin D1 promoter, suggesting that this compound inhibited the expression of Wnt/β-catenin signaling target genes. Further, we found that other NSAIDs including indomethacin, resveratrol, and SC-560 induced apoptosis and suppressed the expression of survivin and the Wnt/β-catenin signaling pathway in HCT-116 cells, indicating that these effects were likely to be common among NSAIDs. Moreover, NSAIDs (celecoxib, SC-560 and indomethacin) also suppressed the expression of cyclin D1 and survivin on other colon cancer cell lines (DLD-1 and SW-620). Our results suggested that NSAIDs could inhibit proliferation and induce apoptosis in colon cancer cells by inhibition of survivin expression and the Wnt/β-catenin signaling pathway.

Original languageEnglish
Pages (from-to)1318-1329
Number of pages12
JournalBiochemical Pharmacology
Issue number9
Publication statusPublished - May 1 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology


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