Newly synthesized curcumin analog has improved  potential to prevent colorectal carcinogenesis in vivo.
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.
Shibata
Hiroyuki
H
Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. hiroyuki@idac.tohoku.ac.jp
Yamakoshi
Hiroyuki
H
Sato
Atsuko
A
Ohori
Hisatsugu
H
Kakudo
Yuichi
Y
Kudo
Chieko
C
Takahashi
Yayoi
Y
Watanabe
Mika
M
Takano
Hiroshi
H
Ishioka
Chikashi
C
Noda
Tetsuo
T
Iwabuchi
Yoshiharu
Y
D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D003474:Curcumin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D015996:Survival Rate; D051176:beta Catenin / Q000378:metabolism
C541015:1,5-bis(3,5-bis(methoxymethoxy)phenyl)penta-1,4-dien-3-one; D001555:Benzene Derivatives; D007659:Ketones; D051176:beta Catenin; D003474:Curcumin