title: Development of pyrrole-imidazole polyamide for specific regulation of human aurora kinase-A and -B gene expression.
abstract: Pyrrole-imidazole polyamide (PIP) is a nuclease-resistant novel compound that inhibits gene expression through binding to the minor groove of DNA. Human aurora kinase-A (AURKA) and -B (AURKB) are important regulators in mitosis during the cell cycle. In this study, two specific PIPs (PIP-A and PIP-B) targeting AURKA and AURKB promoter regions were designed and synthesized, and their biological effects were investigated by several in vitro assays. PIP-A and PIP-B significantly inhibited the promoter activities, mRNA expression, and protein levels of AURKA and AURKB, respectively, in a concentration-dependent manner. Moreover, 1:1 combination treatment with both PIPs demonstrated prominent antiproliferative synergy (CI value [ED(50)] = 0.256) to HeLa cells as a result of inducing apoptosis-mediated severe catastrophe of cell-cycle progression. The novel synthesized PIP-A and PIP-B are potent and specific gene-silencing agents for AURKA and AURKB.
authors: Advanced Research Institute for the Sciences and Humanities, Nihon University, Tokyo, Japan. teruyuk@med.nihon-u.ac.jp
authors: Teruyuki
authors: T
authors: Takahashi
authors: Yukihiro
authors: Y
authors: Asami
authors: Eiko
authors: E
authors: Kitamura
authors: Tsukasa
authors: T
authors: Suzuki
authors: Xiaofei
authors: X
authors: Wang
authors: Jun
authors: J
authors: Igarashi
authors: Aiko
authors: A
authors: Morohashi
authors: Yui
authors: Y
authors: Shinojima
authors: Hisao
authors: H
authors: Kanou
authors: Kosuke
authors: K
authors: Saito
authors: Toshiaki
authors: T
authors: Takasu
authors: Hiroki
authors: H
authors: Nagase
authors: Yuichi
authors: Y
authors: Harada
authors: Kazumichi
authors: K
authors: Kuroda
authors: Takayoshi
authors: T
authors: Watanabe
authors: Satoshi
authors: S
authors: Kumamoto
authors: Takahiko
authors: T
authors: Aoyama
authors: Yoshiaki
authors: Y
authors: Matsumoto
authors: Toshikazu
authors: T
authors: Bando
authors: Hiroshi
authors: H
authors: Sugiyama
authors: Chikako
authors: C
authors: Yoshida-Noro
authors: Noboru
authors: N
authors: Fukuda
authors: Nariyuki
authors: N
authors: Hayashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D015195:Drug Design; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009757:Nylons / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D005456:Fluorescent Dyes; D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; D012333:RNA, Messenger; D004247:DNA; C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016650:Fluorescein-5-isothiocyanate