Department of Food and Nutrition, Technical University of Munich, Freising, Germany.
Mol Nutr Food Res. 2010 Jul;54 Suppl 2:S184-95. doi: 10.1002/mnfr.201000086.
Colorectal cancer is a major cause of cancer deaths worldwide with the need for improved therapeutics and adjuvants.
We here tested whether the secondary plant compound flavone affects the development of aberrant crypt foci and microadenomas triggered in C57BL/6J mice by 1,2-dimethylhydrazine. Ten weeks after the last 1,2-dimethylhydrazine injection, flavone was applied at 400 mg/kg body weight over 4 wk by gavage. Flavone was found to increase apoptosis and to reduce the rate of proliferation and aberrant crypt formation. More importantly, development of microadenomas was completely suppressed by flavone. Proteome analysis by 2-DE with mass spectrometric identification of regulated proteins suggests a downregulation of tricarboxylic acid cycle activity in colonocytes with compensation by increased FADH(2) production via a partial beta-oxidation of long-chain fatty acids to meet energy demands. Transcriptome analysis, using a Gene Chip expression array with 24,000 gene probes confirmed the proteome data and moreover revealed the increased expression of various solute transporters, suggesting increased substrate supply to be used for tricarboxylic acid cycle-independent energy production.
In conclusion, changes in the levels of proteins from intermediary metabolism or their encoding mRNAs are linked to flavone-induced apoptosis and the prevention of microadenoma formation in transformed colonocytes of mice.
结直肠癌是全世界癌症死亡的主要原因，需要改进治疗方法和佐剂。
我们在这里测试了植物次级化合物黄酮是否会影响 1,2-二甲基肼引发的 C57BL/6J 小鼠异常隐窝病灶和微腺瘤的发展。在最后一次注射 1,2-二甲基肼 10 周后，通过灌胃给予黄酮 400mg/kg 体重 4 周。发现黄酮能增加细胞凋亡，降低增殖和异常隐窝形成的速度。更重要的是，黄酮完全抑制了微腺瘤的发展。通过 2-DE 结合质谱鉴定调控蛋白的蛋白质组分析表明，结肠细胞中的三羧酸循环活性下调，通过长链脂肪酸的部分β氧化产生更多的 FADH(2)来补偿，以满足能量需求。使用包含 24000 个基因探针的基因芯片表达谱分析进一步证实了蛋白质组数据，并显示各种溶质转运蛋白的表达增加，表明增加了用于三羧酸循环非依赖性能量产生的底物供应。
总之，细胞内代谢中间产物水平或其编码 mRNA 的变化与黄酮诱导的细胞凋亡以及预防小鼠转化结肠细胞中的微腺瘤形成有关。
