Functional analysis of protein disulfide isomerase P5 as anti-cancer target

• Project/Area Number: 26870287
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry; Biological pharmacy
• Research Institution: Kyoto University
• Principal Investigator: HORIBE TOMOHISA 京都大学, 医学(系)研究科(研究院), 講師 (20467468)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: ケミカルバイオロジー / タンパク質 / 分子シャペロン / 生化学

Outline of Final Research Achievements

We performed the functional analysis of protein disulfide isomerase (PDI) P5 in cancer cells using inhibitors to reductase activity of P5, which we previously screened and identified using a chemical compound library. It was found that one of these inhibitors could decrease the secretion levels of soluble MICA from cancer cells. We also examined the effect of the inhibitors on the cancer cells viability, and found that the inhibitors had cytotoxic activity to cancer cells.

Research Products

• [Journal Article] Discovery of protein disulfide isomerase P5 inhibitors that reduce the secretion of MICA from cancer cells. (2014)
  • Author(s): Horibe T, (他3名)
  • Journal Title: ChemBioChem Volume: 15 Issue: 11 Pages: 1599-1606
  • DOI: 10.1002/cbic.201400050
  • Peer Reviewed
• [Presentation] Functional analysis of protein disulfide isomerase P5 as a potent anti-cancer target (2015)
  • Author(s): Horibe T and Kwakami K.
  • Organizer: 第74回日本癌学会学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] Functional analysis of protein disulfide isomerase P5 in cancer cells by simultaneous observation method of both bioluminescence and fluorescence imaging at single cell level (2015)
  • Author(s): Horibe T, (他2名)
  • Organizer: World Molecular Imaging Congress (WMIC) 2015
  • Place of Presentation: Honolulu, USA
  • Year and Date: 2015-09-02
  • Int'l Joint Research
• [Presentation] P5活性阻害剤のスクリーニングおよび癌細胞からのMICAの分泌に与える影響 (2015)
  • Author(s): 堀部智久、(他2名)
  • Organizer: 第62回日本生化学会 近畿支部例会
  • Place of Presentation: 立命館大学びわこ・くさつキャンパス
  • Year and Date: 2015-05-16
• [Presentation] 癌細胞からのMICA分泌を減少させるP5活性阻害剤のスクリーニング (2014)
  • Author(s): 堀部 智久
  • Organizer: 第１回 バイオ・フロンティア・プラットフォームシンポジウム
  • Place of Presentation: 京都大学 医学部・記念講堂
  • Year and Date: 2014-12-01
  • Invited
• [Presentation] Screening and identification of protein disulfide isomerase P5 inhibitors which reduce the secretion of MICA. (2014)
  • Author(s): Horibe T and Kawakami K
  • Organizer: 第73回日本癌学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27