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Abstract Title:

Natural derivatives of curcumin attenuate the Wnt/beta-catenin pathway through down-regulation of the transcriptional coactivator p300.

Abstract Source:

Biochem Biophys Res Commun. 2008 Dec 26;377(4):1304-8. Epub 2008 Nov 10. PMID: 19000900

Abstract Author(s):

Min-Jung Ryu, Munju Cho, Jie-Young Song, Yeon-Sook Yun, Il-Whan Choi, Dong-Eun Kim, Byeoung-Soo Park, Sangtaek Oh

Article Affiliation:

PharmacoGenomics Research Center, Inje University, Busan 614-735, Republic of Korea.

Abstract:

Curcumin, a component of turmeric (Curcuma longa), has been reported to suppress beta-catenin response transcription (CRT), which is aberrantly activated in colorectal cancer. However, the effects of its natural analogs (demethoxycurcumin [DMC] and bisdemethoxycurcumin [BDMC]) and metabolite (tetrahydrocurcumin [THC]) on the Wnt/beta-catenin pathway have not been investigated. Here, we show that DMC and BDMC suppressed CRT that was activated by Wnt3a conditioned-medium (Wnt3a-CM) without altering the level of intracellular beta-catenin, and inhibited the growth of various colon cancer cells, with comparable potency to curcumin. Additionally, DMC and BDMC down-regulated p300, which is a positive regulator of the Wnt/beta-catenin pathway. Notably, THC also inhibited CRT and cell proliferation, but to a much lesser degree than curcumin, DMC, or BDMC, indicating that the conjugated bonds in the central seven-carbon chain of curcuminoids are essential for the inhibition of Wnt/beta-catenin pathway and the anti-proliferative activity of curcuminoids. Thus, our findings suggest that curcumin derivatives inhibit the Wnt/beta-catenin pathway by decreasing the amount of the transcriptional coactivator p300.

Study Type : In Vitro Study

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Sayer Ji
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