Newly synthesized curcumin analog has improved potential to prevent colorectal carcinogenesis in vivo.

Abstract

Curcumin (diferuloylmethane) has chemopreventive and chemotherapeutic potentials against various types of cancers. We have developed a series of curcumin analogs to improve its low bioavailability by enhancing its potentials. The newly synthesized analog GO-Y030 [(1E, 4E)-1,5-bis-(3,5(-bismethoxymethoxyphenyl) penta-1,4-dien-3-one] showed a 30-fold greater growth suppression in vitro via similar molecular mechanisms to curcumin. The availability of this analog was examined by using a mouse model harboring the germ-line mutation of Apc, Apc(580D/+), in vivo. Apc(580D/+) mice had a very limited survival time with an intestinal obstruction due to polyposis. The average tumor number in mice fed GO-Y030 was reduced to 61.2% of those that were fed the basal diet (P < 0.05). Compared with Apc(580D/+) mice fed the basal diet (median survival time = 166.5 days), a significantly prolonged lifespan (213 days) was observed in Apc(580D/+) mice fed GO-Y030. The chemopreventive effect with GO-Y030 was improved, compared with curcumin (191 days). The survival benefit corresponded to the diminished intestinal tumor incidence in Apc(580D/+) mice fed GO-Y030. No adverse reactions were observed, judging from body weight or biochemical data concerning liver and renal damage. Degradation of accumulated beta-catenin with curcumin is one of the major mechanisms of chemoprevention in colorectal carcinogenesis. It was demonstrated that the number of beta-catenin-positive adenoma cells in Apc(580D/+) mice fed GO-Y030 was reduced.

• Authors: Hiroyuki Shibata, Hiroyuki Yamakoshi, Atsuko Sato, Hisatsugu Ohori, Yuichi Kakudo, Chieko Kudo, Yayoi Takahashi, Mika Watanabe, Hiroshi Takano, Chikashi Ishioka, Tetsuo Noda, Yoshiharu Iwabuchi
• Journal: Cancer science (Cancer Sci) Vol. 100 Issue 5 Pg. 956-60 (May 2009) ISSN: 1349-7006 [Electronic] England
• PMID: 19445025 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1,5-bis(3,5-bis(methoxymethoxy)phenyl)penta-1,4-dien-3-one
• Benzene Derivatives
• Ketones
• beta Catenin
• Curcumin

Topics

• Adenoma (metabolism, pathology)
• Animals
• Benzene Derivatives (chemical synthesis, chemistry, pharmacology)
• Cell Transformation, Neoplastic (metabolism, pathology)
• Colorectal Neoplasms (metabolism, pathology, prevention & control)
• Curcumin (chemical synthesis, chemistry, pharmacology)
• Disease Models, Animal
• Genetic Predisposition to Disease
• Ketones (chemical synthesis, chemistry, pharmacology)
• Mice
• Molecular Structure
• Survival Rate
• beta Catenin (metabolism)