Colon Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Colon Cancer, including details on causes, treatment, symptoms.

Diclofenac attenuates Wnt/beta-catenin signaling in colon cancer cells by activation of NF-kappaB.

Cho M, Gwak J, Park S, Won J, Kim DE, Yea SS, Cha IJ, Kim TK, Shin JG, Oh S

PharmcoGenomic Research Center, Inje University, Busan 633-165, Republic of Korea.

The dysregulation of Wnt/beta-catenin signaling and subsequent upregulation of beta-catenin response transcription (CRT) occur frequently in colon cancer cells. Non-steroidal anti-inflammatory drugs (NSAIDs) can repress CRT in colorectal cancer, but little is known about the mechanism of action. We show that the NSAID diclofenac inhibits Wnt/beta-catenin signaling without altering the level of beta-catenin protein and reduces the expression of beta-catenin/TCF-dependent genes. Diclofenac induced the degradation of IkappaBalpha, which increased free nuclear factor kappaB (NF-kappaB) in cells. Also, the ectopic expression of p65, which is a component of NF-kappaB, suppressed CRT. Our findings suggest that diclofenac inhibits Wnt/beta-catenin signaling via the activation of NF-kappaB in colon cancer cells.

Published 9 August 2005 in FEBS Lett, 579(20): 4213-8.
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