Discovery of a new antitumor drug targeting the tumor-stromal cell interactions

• Project/Area Number: 23501321
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Microbial Chemistry Research Foundation
• Principal Investigator: KAWADA Manabu 公益財団法人微生物化学研究会, 微生物化学研究所沼津支所, 主席研究員 (20300808)
• Co-Investigator(Renkei-kenkyūsha): INOUE Hiroyuki 公益財団法人微生物化学研究会, 微生物化学研究所沼津支所, 研究員 (50601548) ; AMEMIYA Masahide 公益財団法人微生物化学研究会, 微生物化学研究所沼津支所, 研究員 (10232000)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 癌 / 生理活性物質 / 間質

Research Abstract

For creation of a new antitumor drug targeting the interactions between tumor cells and the surrounding stromal cells in tumor tissues, we have developed coculture systems of both cells and searched for compounds that modulate the interactions. As a result, we have isolated a new compound, intervenolin, from the culture broth of actinomyces. Intervenolin inhibits the growth of human gastric and colorectal cancer cell lines when cocultured with the respective organ-derived stromal cells more strongly than that of the cancer cells cultured alone. Intervenolin shows antitumor effects against xenograft models of human gastric and colorectal cancer cells in vivo.

Research Products

• [Journal Article] Intervenolin, a new antitumor compound with anti-Helicobacter pylori activity, from Nocardia sp. ML96-86F2. (2013)
  • Author(s): Kawada, M., Inoue, H., Ohba, S., Hatano, M., Amemiya, M., Hayashi, C., Usami, I., Abe, H., Watanabe, T., Kinoshita, N., Igarashi, M., Masuda, T., Ikeda, D., and Nomoto, A.
  • Journal Title: J. Antibiot. Volume: 66 Issue: 9 Pages: 543-548
  • DOI: 10.1038/ja.2013.42
  • NAID: 10031201650
  • Peer Reviewed
• [Journal Article] Synthesis of intervenolin, an antitumor natural quinolone with unusual substituents. (2013)
  • Author(s): Abe, H., Kawada, M., Inoue, H., Ohba, S., Nomoto, A., Watanabe, T., and Shibasaki M.
  • Journal Title: Org. Lett. Volume: 15 Issue: 9 Pages: 2124-2127
  • DOI: 10.1021/ol400587a
  • Peer Reviewed
• [Journal Article] Structure-activity relationship study of intervenolin derivatives: synthesis, antitumor, and anti-Helicobacter pylori activities. (2013)
  • Author(s): Abe, H., Kawada, M., Inoue, H., Ohba, S., Masuda, T., Hayashi, C., Igarashi, M., Nomoto, A., Watanabe, T., and Shibasaki M.
  • Journal Title: Tetrahedron Volume: 69 Issue: 36 Pages: 7608-7617
  • DOI: 10.1016/j.tet.2013.05.033
  • Peer Reviewed
• [Journal Article] Modulation of tumor-stromal cell interactions: a new anti-tumor strategy targeting the tumor microenvironment. (2013)
  • Author(s): Kawada, M., Sakamoto, S., and Nomoto, A.
  • Journal Title: For. Immunopathol. Dis. Ther. Volume: 4 Issue: 1 Pages: 53-62
  • DOI: 10.1615/forumimmundisther.2013008317
• [Journal Article] Decalpenic acid induces early osteoblastic markers in pluripotent mesenchymal cells via activation of retinoic acid receptor gamma. (2012)
  • Author(s): Sakamoto, S., Kojima, F., Momose, I., Kawada, M., Adachi, H., and Nishimura, Y.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 422 Issue: 4 Pages: 751-757
  • DOI: 10.1016/j.bbrc.2012.05.075
  • Peer Reviewed
• [Journal Article] Cleavage mechanism and anti-tumor activity of 3,6-epidioxy-1,10-bisaboladiene isolated from edible wild plants (2012)
  • Author(s): Kimura KI, Sakamoto Y, Fujisawa N, Uesugi S, Aburai N, Kawada M, Ohba SI, Yamori T, Tsuchiya E, Koshino H
  • Journal Title: Bioorg Med Chem Volume: 20(12) Issue: 12 Pages: 3887-3897
  • DOI: 10.1016/j.bmc.2012.04.025
  • Peer Reviewed
• [Presentation] がんと間質の共培養スクリーニングから発見した抗ピロリ菌活性を有する新規抗がん物質Intervenolin (2013)
  • Author(s): 川田学、坂本修一、雨宮昌秀、増田徹、野本明男
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2013-10-04
• [Presentation] 新規化合物NBRI16716Aによるがんー間質相互作用の制御 (2012)
  • Author(s): 川田学、坂本修一、雨宮昌秀、増田徹、野本明男
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌（北海道）
• [Presentation] がんと間質の共培養スクリーニングから発見した抗ピロリ菌活性を有する新規抗がん物質Intervenolin
  • Author(s): 川田学、坂本修一、雨宮昌秀、増田徹、野本明男
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜市）
• [Presentation] Gastric stromal cells upregulate gastric tumor cell growth through IL-6
  • Author(s): 川田学、坂本修一、雨宮昌秀、増田徹、野本明男
  • Organizer: 第７０回日本癌学会学術集会
  • Place of Presentation: 名古屋国際会議場
• [Remarks]
  • URL: http://www.bikaken.or.jp/
• [Remarks] 公益財団法人微生物化学研究会
  • URL: http://www.bikaken.or.jp/
• [Remarks] 公益財団法人微生物化学研究会
  • URL: http://www.bikaken.or.jp/
• [Remarks]
  • URL: http://www.bikaken.or.jp/
• [Patent(Industrial Property Rights)] 新規化合物、その製造方法、及びその用途、並びに、新規微生物 (2013)
  • Inventor(s): 川田学、井上裕幸、大庭俊一、波多野和樹、阿部光、林千草、渡辺匠、五十嵐雅之
  • Industrial Property Rights Holder: 公益財団法人微生物化学研究会
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-035731
  • Filing Date: 2013-02-26
• [Patent(Industrial Property Rights)] 新規化合物、その製造方法、及びその用途、並びに、新規微生物 (2013)
  • Inventor(s): 川田学、井上裕幸、大庭俊一、波多野和樹、阿部光、他３名
  • Industrial Property Rights Holder: 公益財団法人微生物化学研究会
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-035731
  • Filing Date: 2013-02-26