Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane-induced colon carcinogenesis.

Abstract

SCOPE:

Tetrahydrocurcumin (THC), a major metabolite of curcumin (CUR), has been demonstrated to be anti-cancerogenic and anti-angiogenic and prevents type II diabetes. In this present study, we investigated the chemopreventive effects and underlying molecular mechanisms of dietary administration of CUR and THC in azoxymethane (AOM)-induced colon carcinogenesis in mice.

METHODS AND RESULTS:

All mice were sacrificed at 6 and 23 wk, and colonic tissue was collected and examined. We found that dietary administration of both CUR and THC could reduce aberrant crypt foci and polyps formation, while THC showed a better inhibitory effect than CUR. At the molecular level, results from Western blot analysis and immunohistochemistry staining showed that dietary CUR and THC exhibited anti-inflammatory activity by decreasing the levels of inducible NOS and COX-2 through downregulation of ERK1/2 activation. In addition, both dietary CUR and THC significantly decreased AOM-induced Wnt-1 and β-catenin protein expression, as well as the phosphorylation of GSK-3β in colonic tissue. Moreover, dietary feeding with CUR and THC markedly reduced the protein level of connexin-43, an important molecule of gap junctions, indicating that both CUR and THC might interfer with the intercellular communication of crypt cells.

CONCLUSION:

Taken together, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary THC against AOM-induced colonic tumorigenesis.

• Authors: Ching-Shu Lai, Jia-Ching Wu, Shih-Feng Yu, Vladimir Badmaev, Kalyanam Nagabhushanam, Chi-Tang Ho, Min-Hsiung Pan
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 55 Issue 12 Pg. 1819-28 (Dec 2011) ISSN: 1613-4133 [Electronic] Germany
• PMID: 21887819 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Anticarcinogenic Agents
• CTNNB1 protein, mouse
• Wnt1 Protein
• Wnt1 protein, mouse
• beta Catenin
• tetrahydrocurcumin
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, mouse
• Glycogen Synthase Kinase 3
• Curcumin
• Azoxymethane

Topics

• Animals
• Anticarcinogenic Agents (pharmacology)
• Azoxymethane (toxicity)
• Blotting, Western
• Colon (drug effects, metabolism)
• Colonic Neoplasms (chemically induced, prevention & control)
• Curcumin (analogs & derivatives, pharmacology)
• Down-Regulation (drug effects)
• Glycogen Synthase Kinase 3 (genetics, metabolism)
• Glycogen Synthase Kinase 3 beta
• Male
• Mice
• Mice, Inbred ICR
• Phosphorylation
• Wnt1 Protein (genetics, metabolism)
• beta Catenin (genetics, metabolism)