Analysis of anti-cancer effect of PI polyamide, which suppress MYC downstream genes

2013 Fiscal Year Final Research Report

• Project/Area Number: 23501313
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Nihon University
• Principal Investigator: SOMA Masayoshi 日本大学, 医学部, 教授 (30246855)
• Co-Investigator(Kenkyū-buntansha): FUKUDA Noboru 日本大学, 総合科学研究科, 教授 (40267050) ; UENO Takahiro 日本大学, 医学部, 准教授 (40386008) ; FUJIWARA Kyoko 日本大学, 医学部, 助教 (40595708)
• Co-Investigator(Renkei-kenkyūsha): NAGASE Hiroki 千葉県がんセンター, 研究局, 研究所長 (90322073)
• Project Period (FY): 2011 – 2013
• Keywords: ピロール・イミダゾール・ポリアミド / E-box / MYC / 抗腫瘍効果

Research Abstract

Gene amplification and/or overexpression of the transcription factor c-MYC, which binds to E-box (5'-CACGTG-3') present within its numerous target gene promoters, has been observed in many human tumors. In this study, we have designed pyrrole-midazole polyamides (PIP), which could bind to E-box, and investigated their possible effects on human cancer cells. We found that some PIP we designed significantly suppressed growth of osteosarcoma cell MG63 and leukemia cell K562. According to our present results, PIP-treated cells underwent apoptosis and/or G1 arrest. Furthermore, intravenous injection of PIP markedly repressed MG63-derived tumor development in nude mice. Intriguingly, knockdown of the putative PIP target MALAT1 encoding long non-coding RNA remarkably impaired cell growth of MG63 cells. Collectively, our present findings strongly suggest that PIP exerts its tumor-suppressive ability at least in part through the specific down-regulation of MALAT1.

Research Products

• [Journal Article] Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer, a pyrrole-imidazole polyamide, which targets an E-box motif Original Research Article (2014)
  • Author(s): Taniguchi M, Fujiwara K, Nakai Y, Ozaki T, Koshikawa N, Toshio K, Kataba M, Oguni A, Matsuda H, Yoshida Y, Tokuhashi Y, Fukuda N, Ueno T, Soma M, Nagase H
  • Journal Title: FEBS Open Bio Volume: (4) Pages: 328-334
  • Peer Reviewed
• [Presentation] 抗腫瘍効果を持つE-box 認識ピロール・イミダゾール・ポリアミドの開発 (2013)
  • Author(s): 藤原恭子、相馬正義、永瀬浩喜
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20131003-05
• [Presentation] E-box 認識PI ポリアミドによる抗腫瘍効果の検討 (2013)
  • Author(s): 藤原恭子
  • Organizer: 第22回癌病態治療研究会
  • Place of Presentation: 東京
  • Year and Date: 20130627-28
• [Presentation] Development of a novel E-box binding PI polyamide inhibiting cell-proliferation (2012)
  • Author(s): Fujiwara K, Taniguchi M, Soma M and Nagase H
  • Organizer: 第2回日中がん研究シンポジウム
  • Place of Presentation: 千葉
  • Year and Date: 20120509-11
• [Presentation] ヒト骨肉腫におけるhTERT 遺伝子を標的とした遺伝子発現抑制薬ピロールイミダゾールポリアミドの開発 (2011)
  • Author(s): 谷口真史、藤原恭子、永瀬浩喜、大幸俊三、吉田行弘、大幸英至、小島敏雄、徳橋泰明
  • Organizer: 第26回日本整形外科学会基礎学術集会
  • Place of Presentation: 群馬
  • Year and Date: 20111020-21