Angiotensin II type1 receptor blocker(ARB) Inhibits colon cancer cell proliferation

• Project/Area Number: 23790802
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Nagoya City University
• Principal Investigator: MIZUSHIMA Takashi 名古屋市立大学, 医学(系)研究科(研究院), 研究員 (60433223)
• Research Collaborator: 尾関 啓司 名古屋市立大学, 大学院医学研究科・臨床, 研究医
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: IBD / colitic cancer / AT1R / ARB / telmisarn / telmisartan / NF-κB

Research Abstract

It is known that a disintegrin and metalloproteinase (ADAM) cleaves pro-heparin-binding epidermal growth factor-like growth factor (proHB-EGF), and the soluble HB-EGF activates EGFR. Simultaneously, the C-terminal fragment of proHB-EGF (HB-EGF-CTF) translocates into the inner nuclear membrane, and subsequently influences cell proliferation by binding nuclear promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional repressor, which induces its nuclear export.
We found that colon cancer cell proliferation is regulated via the nuclear translocation of HB-EGF C-terminal fragments. And we also found that telmisartan and its derivatives with biphenyl tetrazole completely blocked this association. We propose that the inhibition of HB-EGF-CTF nuclear translocation with telmisartan and its derivatives may lead to novel strategies that prevent cell proliferation in the development of colon cancer.

Research Products

• [Journal Article] Telmisartan inhibits cell proliferation by blocking nuclear translocation of ProHB-EGF C-terminal fragment in colon cancer cells. (2013)
  • Author(s): Ozeki K, Tanida S, Morimoto C, Inoue Y, Mizoshita T, Tsukamoto H, Shimura T, Kataoka H, Kamiya T, Nishiwaki E, Ishiguro H, Higashiyama S, Joh T.
  • Journal Title: PLoS One Volume: 8(2) Issue: 2 Pages: e56770-e56770
  • DOI: 10.1371/journal.pone.0056770
  • URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579940/
  • Peer Reviewed
• [Presentation] 大腸癌増殖シグナルHB-EGF-C 末端核移行をターゲットとした新規薬剤探索 (2012)
  • Author(s): 尾関 啓司
  • Organizer: 第50回日本癌治療学会学術集会
  • Place of Presentation: 横浜市西区 パシフィコ横浜
  • Year and Date: 2012-10-25
• [Presentation] 炎症性サイトカイン(IL-8) によるHB-EGF-C 末端核移行シグナルを介した大腸細胞増殖機序 (2012)
  • Author(s): 尾関啓司、谷田論史、塚本宏延、片岡洋望、城卓志
  • Organizer: 第40回日本潰瘍学会
  • Place of Presentation: 東京都新宿区 京王プラザホテル
  • Year and Date: 2012-07-14
• [Presentation] Nuclear Translocation of proHB-EGF C-Terminal Fragment Regulates IL-8-Induced Cell Proliferation in Colon Epithelial Cells (2012)
  • Author(s): Keiji Ozeki, Satoshi Tanida, Tsutomu Mizoshita, Hironobu Tsukamoto, Takaya Shimura, Hiromi Kataoka, Takeshi Kamiya, and Takashi Joh
  • Organizer: DDW2012
  • Place of Presentation: San Diego
  • Year and Date: 2012-05-21