title: Stilbene derivatives promote Ago2-dependent tumour-suppressive microRNA activity.
abstract: 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.
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Hagiwara
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kosaka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Ryou-U
authors.initials: RU
authors.lastname: Takahashi
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Takeshita
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D035683:MicroRNAs; D013267:Stilbenes