Celecoxib-induced degradation of T-cell factors-1 and -4 in human colon cancer cells.
We examined the effect of celecoxib on the expression of T-cell factors (TCFs) to clarify the mechanism by which celecoxib suppress beta-catenin/TCF-dependent transcriptional activity without reducing the level of beta-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. Beta-catenin/TCF-dependent transcriptional activity was significantly decreased after the treatment with celecoxib for 6 h 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/beta-catenin signaling pathway induced by celecoxib.
Takahashi-Yanaga
Fumi
F
Department of Clinical Pharmacology, Faculty of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. yanaga@clipharm.med.kyushu-u.ac.jp
Yoshihara
Tatsuya
T
Jingushi
Kentaro
K
Miwa
Yoshikazu
Y
Morimoto
Sachio
S
Hirata
Masato
M
Sasaguri
Toshiyuki
T
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D061988:Proteasome Inhibitors; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D051822:T Cell Transcription Factor 1 / Q000378:metabolism*; D051820:TCF Transcription Factors / Q000378:metabolism*; D058118:Transcription Factor 7-Like 2 Protein; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D061988:Proteasome Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051822:T Cell Transcription Factor 1; D051820:TCF Transcription Factors; C497576:TCF7 protein, human; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D051153:Wnt Proteins; D051176:beta Catenin; D000068579:Celecoxib; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde