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

• Published in: Biochemical and biophysical research communications 2008-12, Vol.377 (4), p.1304-1308
• Main Authors: Ryu, Min-Jung, Cho, Munju, Song, Jie-Young, Yun, Yeon-Sook, Choi, Il-Whan, Kim, Dong-Eun, Park, Byeoung-Soo, Oh, Sangtaek
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; beta Catenin - antagonists & inhibitors; beta Catenin - genetics; Bisdemethoxycurcumin; Cell Line; Cell Line, Tumor; Cell Proliferation - drug effects; Colonic Neoplasms - metabolism; Curcuma longa; Curcumin - analogs & derivatives; Curcumin - chemistry; Curcumin - pharmacology; Demethoxycurcumin; Diarylheptanoids; Down-Regulation; Humans; p300; p300-CBP Transcription Factors - antagonists & inhibitors; p300-CBP Transcription Factors - metabolism; Wnt Proteins - antagonists & inhibitors; Wnt Proteins - genetics; Wnt/β-catenin pathway
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.10.171

Curcumin, a component of turmeric (Curcuma longa), has been reported to suppress β-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/β-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 β-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/β-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/β-catenin pathway and the anti-proliferative activity of curcuminoids. Thus, our findings suggest that curcumin derivatives inhibit the Wnt/β-catenin pathway by decreasing the amount of the transcriptional coactivator p300.