Author/Authors :
Teruyuki Takahashi، نويسنده , , Yukihiro Asami، نويسنده , , Eiko Kitamura، نويسنده , , Tsukasa Suzuki، نويسنده , , Xiaofei Wang، نويسنده , , Jun Igarashi، نويسنده , , Aiko Morohashi، نويسنده , , Yui Shinojima، نويسنده , , Hisao Kanou، نويسنده , , Kosuke Saito، نويسنده , , Toshiaki Takasu، نويسنده , , Hiroki Nagase، نويسنده , , Yuichi Harada، نويسنده , , Kazumichi Kuroda، نويسنده , , Takayoshi Watanabe، نويسنده , , Satoshi Kumamoto، نويسنده ,
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 [ED50] = 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.
