Newly synthesized curcumin analog has improved potential to prevent colorectal carcinogenesis in vivo
Newly synthesized curcumin analog has improved potential to prevent colorectal carcinogenesis in vivo
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DOI：
10.1111/j.1349-7006.2009.01127.x
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发表时间：
2009-05-01
期刊：
影响因子：
5.7
通讯作者：
Iwabuchi, Yoshiharu
中科院分区：
文献类型：
--
作者：
Shibata, Hiroyuki;Yamakoshi, Hiroyuki;Iwabuchi, Yoshiharu
姜黄素（二阿魏酰甲烷）对各种类型的癌症具有化学预防和化学治疗潜力。我们已经开发了一系列姜黄素类似物，以改善其低生物利用度，提高其潜力。新合成的类似物GO-Y 030 [（1 E，4 E）-1，5-bis-（3，5（-bismethoxymethoxyphenyl）penta-1，4-dien-3-one]通过与姜黄素相似的分子机制在体外显示出30倍的生长抑制作用。通过使用携带Apc的种系突变Apc（580 D/+）的小鼠模型在体内检查该类似物的可用性。Apc（580 D/+）小鼠因息肉病导致肠梗阻的存活时间非常有限。喂食GO-Y 030的小鼠的平均肿瘤数量减少到喂食基础饮食的小鼠的61.2%（P < 0.05）。与喂食基础饮食的Apc（580 D/+）小鼠（中位存活时间= 166.5天）相比，在喂食GO-Y 030的Apc（580 D/+）小鼠中观察到显著延长的寿命（213天）。与姜黄素（191天）相比，GO-Y 030的化学预防效果有所改善。存活益处对应于喂食GO-Y 030的Apc（580 D/+）小鼠中肠肿瘤发生率的降低。根据体重或有关肝和肾损害的生化数据判断，未观察到不良反应。姜黄素降解积聚的β-连环蛋白是大肠癌化学预防的主要机制之一。证明了喂食GO-Y 030的Apc（580 D/+）小鼠中β-连环蛋白阳性腺瘤细胞的数量减少。（Cancer Sci 2009; 100：956-960）。
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. (Cancer Sci 2009; 100: 956-960).