Basic research on the development of novel anticancer drugs utilizing bioactive substances from insects

• Project/Area Number: 20380039
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied entomology
• Research Institution: National Institute of Agrobiological Sciences
• Principal Investigator: YAMAKAWA Minoru 独立行政法人農業生物資源研究所, 昆虫科学研究領域, 特任上級研究員 (30183677)
• Project Period (FY): 2008 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2011: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2010: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2009: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2008: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
• Keywords: 昆虫 / 抗がん剤 / がん細胞 / 増殖抑制活性 / 新規化合物 / がん細胞増殖抑制メカニズム / タカサゴシロアリ / がん細胞増殖抑制活性 / 精製 / 構造解析 / 昆虫利用 / 機能開発 / 抗ガン剤 / 抗生物ペプチド / 改変 / ガン細胞 / 作用機構 / ミトコンドリア / 細胞内移行 / 抗微生物ペプチド / 作用標的 / マウス骨髄腫

Research Abstract

The purpose of this study was to clarify the mode of action of beetle-derived antimicrobial peptides which attack some cancer cells but not normal cells. The peptides were revealed to electrostatically interact with negatively charged phosphatidylserine and disrupt the membrane of some cancer cells. On the other hand, a new compound, 1,1’-biphenyl-3,3’,4-triol was isolated and identified from a termite, Nasutitermes takasagoensis (Shiraki). This compound showed the suppressing activity of cancer cell proliferation, and the mode of action was suggested to be different from those of already-known anticancer drugs

Research Products

• [Journal Article] Anti-angiogenesis activities of novel peptide complexes: mitochondria disruptive 9-mer peptides conjugated with integrin alpha V beta 3-homing cyclic RGD motif (2012)
  • Author(s): Iwasaki, T., Yamakawa, M., Asaoka, A., Kawano, T. and Ishibashi, J
  • Journal Title: Biosci. Biotechnol. Biochem Volume: 76 Pages: 2044-2048
  • NAID: 10031126505
  • Peer Reviewed
• [Journal Article] Anti-angiogenesis activities of novel peptide complexes: mitochondria disruptive 9-mer peptides conjugated with integrin alpha V beta 3-homing cyclic RGD motif. (2012)
  • Author(s): Iwasaki, T., Yamakawa, M., Asaoka, A., Kawano, T. and Ishibashi, J.
  • Journal Title: Bioscience Biotechinology and Biochemistry Volume: 76 Pages: 2044-2048
  • NAID: 10031126505
  • Peer Reviewed
• [Journal Article] 昆虫抗微生物ペプチドを用いた生体防御研究―改変ペプチドの抗菌・抗ガン活性と作用機構― (2010)
  • Author(s): 山川 稔、岩崎 崇、石橋 純
  • Journal Title: 感染・炎症・免疫 Volume: 40 Pages: 6-15
• [Journal Article] 昆虫抗微生物ペプチドを用いた生体防御研究-改変ペプチドの抗菌・抗ガン活性と作用機構- (2010)
  • Author(s): 山川稔、岩崎崇、石橋純
  • Journal Title: 感染・炎症・免疫 40 Pages: 6-15
• [Journal Article] 昆虫抗微生物ペプチドを用いた生体防御研究-改変ペプチドの抗菌・抗ガン活性と作用機構- (2010)
  • Author(s): 山川稔、岩崎崇、石橋純
  • Journal Title: 感染・炎症・免疫 Volume: 40 Pages: 6-15
• [Journal Article] Selective cancer cell cytotoxicity of enantiomeric 9-mer peptides derived from beetle defensins depends on negatively charged phosphatidylserine on the cell surface (2009)
  • Author(s): Iwasaki, T., Ishibashi, J., Saido-Sakanaka, H., Tanaka, H., Sato, M., Taylor, D. and Yamakawa, M
  • Journal Title: Peptides Volume: 30 Pages: 660-668
  • Peer Reviewed
• [Journal Article] Multiple functions of short enantiomeric peptides based on beetle defensins (2009)
  • Author(s): Iwasaki, T., Ishibashi, J., Kubo, M., Taylor, D. and Yamakawa, M
  • Journal Title: Biosci. Biotechnol. Biochem Volume: 73 Pages: 683-687
  • Peer Reviewed
• [Journal Article] Antibacterial and anticancer activity of diasteromeric 9-mer peptides derived from beetle defensins (2009)
  • Author(s): Iwasaki, T., Ishibashi, J., Taanaka, H., Sato, M., Asaoka, A., Taylor, D. and Yamakawa, M
  • Journal Title: Peptide Science Volume: 2008 Pages: 51-59
  • Peer Reviewed
• [Journal Article] Selective cancer cell cytotoxicity of enantiomeric 9-mer peptides derived from beetle defensins depends on negatively charged phosphadidylserine on the cell surface. (2009)
  • Author(s): Iwasaki, T., Ishibashi, J., Saido-Sakanaka, H., Tanaka, H., Sato, M., Asaoka, A., Taylor, D.,Yamakawa, M
  • Journal Title: Peptides 30 Pages: 660-668
  • Peer Reviewed
• [Journal Article] Multiple functions of short enantiomeric peptides based on beetle defensins. (2009)
  • Author(s): Iwasaki, T., Ishibashi, J., Kubo, M., Taylor, D., Yamakawa, M.
  • Journal Title: Biosci.Biotechnol. Biochem. 73 Pages: 683-687
  • Peer Reviewed
• [Journal Article] Multi-target of enantiomeric 9-mer peptides derived from beetle defensins. (2009)
  • Author(s): Iwasaki, T., Ishibashi, J., Tanaka, H., Sato, M., Asaoka, A., Taylor, D., Yamakawa, M.
  • Journal Title: Peptide Science 2008 Pages: 51-59
  • NAID: 10027165909
  • Peer Reviewed
• [Journal Article] Multiple functions of short enantiomeric peptides based on beetle defensins (2009)
  • Author(s): Iwasaki, T., Ishibashi, J., Kubo, M., Taylor, D., Yamakawa, M.
  • Journal Title: Biosci.Biotechnol.Biochem. 73 Pages: 683-687
  • Peer Reviewed
• [Journal Article] Multi-target of enantiomeric 9-mer peptides derived from beetle defensins (2009)
  • Author(s): Iwasaki, T., Ishibashi, J., Tanaka, H., Sato, M., Asaoka, A, Taylor, D., Yamakawa, M.
  • Journal Title: Peptide Science 2008 Pages: 51-54
  • NAID: 10027165909
  • Peer Reviewed
• [Journal Article] Selective cancer cell cytotoxicity of enantiomeric 9-mer peptides derived from beetle defensins depends on negatively charged phosphatidylserine on the cell surface (2009)
  • Author(s): Iwasaki, T., Ishibashi, J, Tanaka, H., Sato, M., Asaoka, A., Taylor, D. Yamakawa, M.
  • Journal Title: Peptides 30 Pages: 660-668
  • Peer Reviewed
• [Journal Article] Antibacterial and anticancer activity of diasteromeric 9-mer peptides derived from beetle defensins (2008)
  • Author(s): Iwasaki, T., Ishibashi, J., Saido-Sakanaka, H., Sato, M., Asaoka, A., Taylor, D. and Yamakawa, M
  • Journal Title: Peptide Science Volume: 2007 Pages: 79-82
  • Peer Reviewed
• [Journal Article] Antibacterial and anticancer activity of diasteromeric 9-mer peptides derived from beetle defensins. (2008)
  • Author(s): Iwasaki, T., Ishibashi, J., Saido-Sakanaka, H., Tanaka, H., Sato, M., Asaoka, A., Taylor, D.,Yamakawa, M.
  • Journal Title: Peptide Science 2007 Pages: 79-82
  • Peer Reviewed
• [Journal Article] Antibacterial and anticancer activity of diasteromeric 9-mer peptides derived from beetle defensins (2008)
  • Author(s): Iwasaki, T., Ishibashi, J., Saido-Sakanaka, H., Tanaka, H., Sato, M., Asaoka, A., Taylor, D., Yamakawa, M.
  • Journal Title: Peptide Science 2007 Pages: 79-82
  • Peer Reviewed
• [Presentation] 昆虫抗微生物タンパク質改変ペプチドのリン脂質膜との相互作用 (2013)
  • Author(s): 石橋 純、山川 稔他
  • Organizer: 平成25年度度蚕糸・昆虫機能利用学術講演会
  • Place of Presentation: 茨城
  • Year and Date: 2013-03-18
• [Presentation] 昆虫抗微生物タンパク質改変ペプチドのリン脂質膜との相互作用 (2013)
  • Author(s): 石橋 純その他７人
  • Organizer: 日本蚕糸学会
  • Place of Presentation: 農林水産技術会議事務局筑波事務所（つくば市）
• [Presentation] タカサゴシロアリ由来ガン細胞増殖抑制物質の探索と同定 (2012)
  • Author(s): 石橋 純、山川 稔他
  • Organizer: 平成23年度蚕糸・昆虫機能利用学術講演会
  • Place of Presentation: 福岡
  • Year and Date: 2012-03-19
• [Presentation] タカサゴシロアリ由来ガン細胞増殖抑制物質の探索と同定 (2012)
  • Author(s): 石橋純、米田泰崇、亀山眞由美、吉田充、山川稔
  • Organizer: 日本蚕糸学会第82回大会
  • Place of Presentation: 九州大学(福岡市)
  • Year and Date: 2012-03-19
• [Presentation] Multi-target of enanteromeric 9-mer peptides derived from beetle defensins (2009)
  • Author(s): Iwasaki, T., Yamakawa, M. et al.
  • Organizer: 2009 Keystone Symposia
  • Place of Presentation: カナダ、ウイスラー
  • Year and Date: 2009-03-29
• [Presentation] カブトムシディフェンシン由来改変ペプチドの多機能解析 (2009)
  • Author(s): 岩崎 崇、山川 稔他
  • Organizer: 平成21年度蚕糸・昆虫機能利用学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-21
• [Presentation] Mitochondria disruptive 9-mer peptides conjugated with tumor homing domain: cyclic RGD motif (2009)
  • Author(s): Iwasaki, T., Yamakawa, M. et al.
  • Organizer: 第46回ペプチド討論会
  • Place of Presentation: 北九州市
• [Presentation] Mitochondoria disruptive 9-mer peptides conjugated with tumor homing domain : cyclic RGD motif (2009)
  • Author(s): Iwasaki, T., Yamakawa, M., et al.
  • Organizer: 第46回ペプチド討論会
  • Place of Presentation: 北九州市
• [Presentation] Mitochondoria disruptive 9-mer peptides conjugated with tumor homing domain : cyclic RGD motif (2009)
  • Author(s): Iwasaki, T., Asaoka, A., Yamakawa, M., Ishibashi, J.
  • Organizer: 第46回ペプチド討論会
  • Place of Presentation: 北九州国際会議場、北九州市
• [Presentation] Multi-target of enanteromeric 9-mer peptides derived from beetle defensins (2008)
  • Author(s): Iwasaki, T., Yamakawa, M. et al.
  • Organizer: 日本ペプチド学会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-29
• [Presentation] Multi-target of enanteromeric 9-mer peptides derived from beetle defensins. (2008)
  • Author(s): Iwasaki, T., Yamakawa, M., et al.
  • Organizer: 日本ペプチド学会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-29
• [Presentation] カブトムシディフェンシン由来改変ペプチドのマルチターゲット (2008)
  • Author(s): 岩崎 崇、山川 稔他
  • Organizer: 第41回若手ペプチド夏の勉強会
  • Place of Presentation: 京都
  • Year and Date: 2008-08-04
• [Patent(Industrial Property Rights)] 新規ビフェニール化合物 (2010)
  • Inventor(s): 亀山真由美、石橋純、山川稔、米田泰崇、吉田充
  • Industrial Property Rights Holder: 農業生物資源研究所、食品総合研究所
  • Industrial Property Number: 2010-164384
  • Filing Date: 2010-07-21
• [Patent(Industrial Property Rights)] 新規ビフェニール化合物 (2010)
  • Inventor(s): 亀山真由美、石橋純、山川稔、米田泰崇、吉田充
  • Industrial Property Rights Holder: 農業生物資源研究所、食品総合研究所
  • Filing Date: 2010-07-21
• [Patent(Industrial Property Rights)] 新規ビフェニール化合物 (2010)
  • Inventor(s): 亀山真由美、石橋純、山川稔、米田泰崇、吉田充
  • Industrial Property Rights Holder: 農業生物資源研究所、食品総合研究所
  • Filing Date: 2010-07-21