Research Abstract


Stilbene derivatives promote Ago2-dependent tumour-suppressive microRNA activity

2012年3月15日 Scientific Reports 2 : 314 doi: 10.1038/srep00314


萩原 啓太郎1,2, 小坂 展慶1, 吉岡 祐亮1, 高橋陵宇1, 竹下 文隆1 & 落谷 孝広1,2

  1. 国立がん研究センター研究所 分子細胞治療研究分野
  2. 東京工業大学 大学院生命理工学研究科
It is well known that natural products are a rich source of compounds for applications in medicine, pharmacy, and biology. However, the exact molecular mechanisms of natural agents in human health have not been clearly defined. Here, we demonstrate for the first time that the polyphenolic phytoalexin resveratrol promotes expression and activity of Argonaute2 (Ago2), a central RNA interference (RNAi) component, which thereby inhibits breast cancer stem-like cell characteristics by increasing the expression of a number of tumour-suppressive miRNAs, including miR-16, -141, -143, and -200c. Most importantly, resveratrol-induced Ago2 resulted in a long-term gene silencing response. We also found that pterostilbene, which is a natural dimethylated resveratrol analogue, is capable of mediating Ago2-dependent anti-cancer activity in a manner mechanistically similar to that of resveratrol. These findings suggest that the dietary intake of natural products contributes to the prevention and treatment of diseases by regulating the RNAi pathway.