TY - JOUR
T1 - Celecoxib-induced degradation of T-cell factors-1 and -4 in human colon cancer cells
AU - Takahashi-Yanaga, Fumi
AU - Yoshihara, Tatsuya
AU - Jingushi, Kentaro
AU - Miwa, Yoshikazu
AU - Morimoto, Sachio
AU - Hirata, Masato
AU - Sasaguri, Toshiyuki
PY - 2008/12/26
Y1 - 2008/12/26
N2 - 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 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/β-catenin signaling pathway induced by celecoxib.
AB - 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 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/β-catenin signaling pathway induced by celecoxib.
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U2 - 10.1016/j.bbrc.2008.10.115
DO - 10.1016/j.bbrc.2008.10.115
M3 - Article
C2 - 18983819
AN - SCOPUS:56349123769
SN - 0006-291X
VL - 377
SP - 1185
EP - 1190
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -