Studies on the mechanisms of anticancer and anti-inflammatory activities of alkaloids from ascidians

2011 Fiscal Year Final Research Report

• Project/Area Number: 21603012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Tohoku Pharmaceutical University
• Principal Investigator: NAMIKOSHI Michio 東北薬科大学, 薬学部, 教授 (30189196)
• Co-Investigator(Renkei-kenkyūsha): NAKAZAWA Takahiro 東北薬科大学, 薬学部, 講師 (60296019) ; UKAI Kazuyo 東北薬科大学, 薬学部, 助教 (60433512) ; YAMAZAKI Hiroyuki 東北薬科大学, 薬学部, 助手 (70525344)
• Project Period (FY): 2009 – 2011
• Keywords: ホヤ / アルカロイド / 抗癌活性 / 抗炎症活性 / 生物活性発現機構 / TNF-α / NF-κB / α-カルボリン

Research Abstract

Lissoclibadins, anticancer alkaloids isolated from an Indonesian colonial ascidian, induced an apoptosis(programmed cell death) to cancer cells by increasing the activity of caspases, important proteins for the induction of an apoptosis. Two alkaloids were isolated from a sponge collected in Iriomote Is., Okinawa as cytotoxic components, which induced an apoptosis to cancer cells. DDMG-1, an alkaloid isolated from an Indonesian solitary ascidian, decreased the production of TNF-α, an inflammatory cytokine that over produced in rheumatism and cancer, and the molecular mechanism of action was elucidated. Three components, which inhibited the production of TNF-α, were isolated from an Indonesian soft coral.

Research Products

• [Journal Article] Papuamine and haliclonadiamine, obtained from an Indonesian sponge Haliclona sp (2012)
  • Author(s): H. Yamazaki, D. S. Wewengkang, S. Kanno, M. Ishikawa, Henki Rotinsulu, R. E. P. Mangindaan, M. Namikoshi
  • Journal Title: Nat. Prod. Res Volume: (in press)
  • DOI: DOI:10.1080/14786419.2012.688050
  • Peer Reviewed
• [Journal Article] Two New Tryptamine Derivatives, Leptoclinidamide and(-)-Leptoclinidamine B from an Indonesian Ascidian Leptoclinides dubius (2012)
  • Author(s): H. Yamazaki, D. S. Wewengkang, T. Nishikawa, H. Rotinsulu, R. E. P. Mangindaan, M. Namikoshi
  • Journal Title: Mar. Drugs Volume: 10 Pages: 349-357
  • DOI: DOI:10.3390/md10020349
  • Peer Reviewed
• [Journal Article] Lobohedleolide induces interleukin-8 production in LPS-stimulated human monocytic cell line THP-1 (2011)
  • Author(s): T. Oda, D. S. Wewengkang, M. M. Kapojos, R. E. P. Mangindaan, J.-S. Lee, M. Namikoshi
  • Journal Title: Int. J. Appl. Res. Nat. Prod Volume: 4 Pages: 16-21
  • URL: http://www.doaj.org/
  • Peer Reviewed
• [Journal Article] Two unprecedented cembrane-type terpenes from an Indonesian soft coral Sarcophyton sp (2010)
  • Author(s): M. M. Kapojos, J.-S. Lee, T. Oda, T. Nakazawa, O. Takahashi, K. Ukai, R. E. P. Mangindaan, H. Rotinsulu, D. S. Wewengkang, S. Tsukamoto, H. Kobayashi, M. Namikoshi
  • Journal Title: Tetrahedron Volume: 66 Pages: 641-645
• [Journal Article] Lissoclibadins 8.14, polysulfur dopaminederived alkaloids from the colonial ascidian Lissoclinum cf (2009)
  • Author(s): W. Wang, O. Takahashi, T. Oda, T. Nakazawa, K. Ukai, R. E. P. Mangindaan, H. Rotinsulu, D. S. Wewengkang, H. Kobayashi, S. Tsukamoto, M. Namikoshi
  • Journal Title: Tetrahedron Volume: 65 Pages: 9598-9603
  • DOI: DOI:10.1016/j.tet.2009.09.056
  • Peer Reviewed
• [Journal Article] Inhibitory Effect of N, N-Didesmethylgrossularine-1 on Inflammatory Cytokine Production in Lipopolysaccharide-stimulated RAW 264.7 Cells (2009)
  • Author(s): T. Oda, J.-S. Lee, Y. Sato, S. Sakamoto, H. Handa, R. E. P. Mangindaan, M. Namikoshi
  • Journal Title: Mar. Drugs Volume: 7 Pages: 589-599
  • DOI: DOI:10.3390/md7040589
  • Peer Reviewed
• [Presentation] インドネシア産群体ボヤから単離した新規インドールアルカロイドの構造 (2012)
  • Author(s): 山崎寛之、D. S. Wewengkang、西川輝昭、H. Rotinsulu、R. E. P. Mangindaan、浪越通夫、
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] インドネシア産海綿から単離したpapuamine類のアポトーシス誘導作用 (2012)
  • Author(s): 山崎寛之, 菅野秀一, D. S. Wewengkang, 石川正明、H. Rotinsulu, R. E. P. Mangindaan, 浪越通夫
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] 海洋天然物13種のV79細胞に対する細胞障害性について (2012)
  • Author(s): 小田泰子, 北村美里, 山崎寛之, R. E. P. Mangindaan, 浪越通夫
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-30
• [Presentation] 炎症性サイトカイン産生系に効果を示す海洋天然物の探索 (2012)
  • Author(s): 小田泰子, 北村美里, 山崎寛之, R. E. P. Mangindaan, 浪越通夫
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-29
• [Presentation] Bioactive Compounds from Indonesian Ascidian Leptoclinides dubius and Marine Sponge Haliclona sp (2012)
  • Author(s): H. Yamazaki, D. S. Wewengkang, S. Kanno, T. Nishikawa, H. Rotinsulu, M. Ishikawa, R. E. P. Mangindaan, M. Namikoshi
  • Organizer: The 6th Korea-Japan Chemical Biology Symposium
  • Place of Presentation: 札幌
  • Year and Date: 2012-01-27
• [Presentation] インドネシア産単体ボヤから単離した新規化合物の構造 (2011)
  • Author(s): 山崎寛之, D. S. Wewengkang, H. Rotinsulu, R. E. P. Mangindaan, 塚本佐知子、浪越通夫
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-30
• [Presentation] LPS刺激したRAW 264.7細胞による炎症性サイトカインの産生へのmagnololの影響 (2011)
  • Author(s): 小田泰子、北村美里、中澤孝浩、浪越通夫
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 2011-03-30
• [Presentation] Regulation of inflammatory cytokine production by lobohedleolide (2010)
  • Author(s): T. Oda, M. Namikoshi
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-26
• [Presentation] 単球系細胞株から産生誘導されるインターロイキン8へのLissoclibadin 1～7の影響 (2010)
  • Author(s): 小田泰子、澤井太郎、浪越通夫、中澤孝浩、鵜飼和代、小林久芳、Remy E. P. Mangindaan
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-29
• [Presentation] 炎症性サイトカイン産生へのlobohedreolideの影響 (2010)
  • Author(s): 浪越通夫、小田泰子、澤井太郎、中沢孝浩、鵜飼和代、小林久芳、R. E. P. Mangindaan
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-29