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Development of the new cancer preventing method with the ingredient of the food of Kyoto

使用京都食品成分开发新的癌症预防方法

基本信息

批准号：
12794011
负责人：
SAKAI Toshiyuki
金额：
$ 25.79万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for University and Society Collaboration
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12794011/
关键词：
Vitamin D_3 p27 NF-Y mac25 gadd45 Sodium Butyrate flavonoids quercetin プロモーターヒストン脱アセチル化酵素阻害剤 p21 WAF1 mac25遺伝子癌予防ビタミンD_3受容体

项目摘要

We showed clearly that the vitamin D_3 which is considered to have a preventive effect on colon cancer and prostatic cancer, etc, contained in the mushroom used abundantly at the food of Kyoto, activates the p27 gene promoter through its Sp1 and CCAAT binding sites by the transcription factors Sp1 and NF-Y, and not through the vitamin D_3 receptor-binding site.Vitamin D_3 also activates mac25, gene, which is known to compensate for the function of tumor-suppressor gene p53.The dietary fiber, which is contained in the root crop used in the food of Kyoto, is metabolized to butyrate. We showed clearly that the butyrate activates the gadd45 gene promoter, in p53-independent manner, through its Oct-1 and CCAAT binding sites by the transcription factors Oct-1 and NF-Y.We searched for another drugs which can activate gadd45 gene promoter from the ingredients of food, such as flavonoids contained in the Kyoto vegetable, green tea, etc., and found that quercetin which is a kind of flavonoid activates gadd45 gene in p53-independent manner. Although this activation was seen in the mRNA level, there was no change in promoter activity. It has suggested that the mechanism of activation of gadd45 gene is different between butyrate and quercetin.Using about 16 gene promoters we have (eg. cell cycle-regulating genes, apoptosis related genes), the promoter-activating drug was searched and some interesting drugs were found out. These drugs are expected to become new cancer preventive drugs.

我们清楚地表明，京都食品中大量使用的蘑菇中含有的被认为对结肠癌和前列腺癌等具有预防作用的维生素D_3，通过转录因子Sp1和NF-Y通过其Sp1和CCAAT结合位点激活p27基因启动子，而不是通过维生素D_3受体结合位点激活。维生素D_3还激活mac25，已知该基因可以补偿肿瘤抑制基因 p53 的功能。京都食品中使用的块根作物中含有的膳食纤维会代谢为丁酸盐。我们清楚地表明丁酸盐通过转录因子Oct-1和NF-Y通过其Oct-1和CCAAT结合位点以不依赖于p53的方式激活gadd45基因启动子。我们从食品成分中寻找另一种可以激活gadd45基因启动子的药物，例如京都蔬菜、绿茶等中含有的黄酮类化合物，并发现槲皮素是一种类黄酮以不依赖 p53 的方式激活 gadd45 基因。尽管这种激活是在 mRNA 水平上观察到的，但启动子活性没有变化。提示丁酸和槲皮素激活gadd45基因的机制不同。利用我们现有的16个基因启动子（如细胞周期调控基因、凋亡相关基因），对启动子激活药物进行了搜索，发现了一些有趣的药物。这些药物有望成为新的癌症预防药物。