The inhibitory potency of peptides derived from autophosphorylation sites of receptor tyrosine kinase in a non-ATP-competitive mechanism on tumor cells.

• Project/Area Number: 22590076
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Himeji Dokkyo University
• Principal Investigator: KURODA Yoshihiro 姫路獨協大学, 薬学部, 教授 (90093236)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: EGFR, IGF1R, 阻害ペプチド / 細胞膜透過性 / チロシンキナーゼ / EGFR / IGF1R / 阻害ペプチド / ATP非競合的作用機序 / 細胞増殖 / 細胞毒性 / カスパーゼ3活性

Research Abstract

Previously, based on amino-acid sequences of autophosphorylation sites of receptor tyrosine kinase such as EGFR and IR, we designed small peptides which inhibit phosphorylation of EGFR or IR effectively. The aim of this study was to observe the effects of these peptides on tumor cells. We found that membrane-permeable synthetic peptides derived from EGF receptor autophosphorylation sites have the potential to suppress EGF receptor function in A549 cells and derived from IGF-1 receptor autophosphorylation sites have the potential to suppress IGF-1 receptor function in MCF-7 cells. These peptides have the potential to be developed into novel and useful agents for cancer therapy.

Research Products

• [Journal Article] Oligopeptides derived from autophosphorylation sites of EGF receptor suppress EGF-stimulated responses in human lung carcinoma A549 cells. (2013)
  • Author(s): Kuroda Y, Kato-Kogoe N, Tasaki E, Murata E, Ueda K, Abe M, Miyamoto K, Nakase I, Futaki S, Tohyama Y, Hirose M.
  • Journal Title: Eur J Pharmacol. Volume: 5 Pages: 87-94
  • Peer Reviewed
• [Journal Article] Oligopeptides derived from autophosphorylation sites of EGF receptor suppress EGF-stimulated responses in human lung carcinoma A549 cells. (2013)
  • Author(s): Kuroda Y, Kato-Kogoe N, Tasaki E, Murata M, Ueda K, Abe M, Miyamoto K, Nakase I, Futaki S, Tohyama Y, Hirose M
  • Journal Title: Eur J Pharmacol Volume: 698 Issue: 1-3 Pages: 87-94
  • DOI: 10.1016/j.ejphar.2012.10.007
  • Peer Reviewed
• [Presentation] EGFRの自己リン酸化部位由来ペプチドのA549ヒト肺腺がん細胞における効果. (2011)
  • Author(s): 黒田義弘、村田恵理、上田康陽、田崎絵美、小越菜保子、阿部峰大、宮本和英、中瀬生彦、二木史朗、通山由美、廣瀬宗孝
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] EGFRの自己リン酸化部位由来ペプチドのA549ヒト肺腺がん細胞における効果 (2011)
  • Author(s): 黒田義弘
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 国立京都国際会館(京都)
  • Year and Date: 2011-09-23
• [Presentation] 細胞透過性オリゴペプチドによるA549ヒト肺腺がん細胞に対する細胞増殖抑制、細胞毒性、及びアポトーシスへの影響 (2011)
  • Author(s): 黒田義弘
  • Organizer: 日本薬学会 第131年会
  • Place of Presentation: ツインメッセ静岡(静岡市)
  • Year and Date: 2011-03-30
• [Presentation] 細胞透過性オリゴペプチドによるA549ヒト肺線がん細胞に体する細胞増殖抑制、細胞毒性、及びアポトーシスへの影響 (2011)
  • Author(s): 黒田義弘、村田恵理、上田康陽、田崎絵美、小越菜保子、阿部峰大、宮本和英、中瀬生彦、二木史朗、通山由美、廣瀬宗孝
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡