Celecoxib-induced degradation of T-cell factors-1 and -4 in human colon cancer cells

• Published in: Biochemical and biophysical research communications 2008-12, Vol.377 (4), p.1185-1190
• Main Authors: Takahashi-Yanaga, Fumi, Yoshihara, Tatsuya, Jingushi, Kentaro, Miwa, Yoshikazu, Morimoto, Sachio, Hirata, Masato, Sasaguri, Toshiyuki
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; beta Catenin - metabolism; Celecoxib; Cell Line, Tumor; Colon cancer cell; Colonic Neoplasms - metabolism; Cysteine Proteinase Inhibitors - pharmacology; Humans; Leupeptins - pharmacology; Proteasome Inhibitors; Pyrazoles - pharmacology; Sulfonamides - pharmacology; T Cell Transcription Factor 1 - metabolism; T-cell factor (TCF); TCF Transcription Factors - metabolism; Transcription Factor 7-Like 2 Protein; Transcription, Genetic; Wnt Proteins - metabolism; Wnt/β-catenin signaling pathway
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.10.115

We examined the effect of celecoxib on the expression of T-cell factors (TCFs) to clarify the mechanism by which celecoxib suppress β-catenin/TCF-dependent transcriptional activity without reducing the level of β-catenin protein, using HCT-116 cells. Celecoxib suppressed the expression of TCF-1 and TCF-4 in a time-dependent manner. Pretreatment of cells with the proteasome inhibitor MG132 inhibited the loss of TCF-1 and TCF-4 induced by celecoxib, suggesting that celecoxib induced the proteasome-dependent degradation of TCF-1 and TCF-4. β-Catenin/TCF-dependent transcriptional activity was significantly decreased after the treatment with celecoxib for 6h and the pretreatment of the cells with MG132 attenuated the effect of celecoxib. Further, celecoxib also suppressed the expression of TCF-1 and TCF-4 in another colon cancer cell line, DLD-1. Our results suggest that TCF-1 and TCF-4 degradation may involve the inhibition of the Wnt/β-catenin signaling pathway induced by celecoxib.