Antitumor natural products targeting PPAR-gamma and their combination effect with clinically used anticancer agents

• Project/Area Number: 25460134
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Natural medicines
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Mimaki Yoshihiro 東京薬科大学, 薬学部, 教授 (90229790)
• Co-Investigator(Kenkyū-buntansha): 松尾 侑希子 東京薬科大学, 薬学部, 助教 (70434016)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: PPAR-gamma / Santalum album / セスキテルペン / 選択的腫瘍細胞毒性 / カンゾウ / プレニルイソフラボノイド誘導体 / ビャクシ / 新規クマリン誘導体 / PPAR-γリガンド活性 / 天然物 / 腫瘍細胞毒性 / 併用効果 / マオウ / ハマボウフウ / フラノクマリン / 培養腫瘍細胞 / HL-60細胞 / A549細胞

Outline of Final Research Achievements

Magnolol, a natural PPAR-gamma agonist, enhanced the tumor selective cytotoxic activity of a new sesquiterpene from Santalum album heart wood against HL-60 leukemia cells by more than 100 times. Furthermore, a prenylisoflavonoid derivative from Glycyrrhiza glabra roots and a new coumarin derivative from Angelica dahurica roots exhibited PPAR-gamma agonist activity and attenuated the cytotoxicity of etoposide, a clinically used anticancer agent, against A549 lung adenocarcinoma cells. The kampo prescription of Shimpito Extract and Ephedra Herb extract showed PPAR-gamma agonist activity. Three prenylfuranocoumarin derivatives were isolated from Glehnia littoralis roots and rhizomes as the PPAR-gamma agonists.

Research Products

• [Journal Article] A rare type of sesquiterpene and β-santalol derivatives from Santalum album and their cytotoxic activities (2014)
  • Author(s): Matsuo, Y.; Sakagami, H.; Mimaki, Y.
  • Journal Title: Chem. Pharm. Bull. Volume: 62 Pages: 1192-1199
  • NAID: 130004712914
  • Peer Reviewed / Open Access
• [Journal Article] Two new homoisoflavonoids from the bulbs of Bessera elegans (2014)
  • Author(s): Matsuo, Y.; Kurihara, R.; Akagi, N.; Mimaki, Y.
  • Journal Title: Nat. Prod. Commun. Volume: 9 Pages: 1725-1727
  • Peer Reviewed
• [Journal Article] ビャクダン抽出物に含有される腫瘍細胞毒性成分 (2014)
  • Author(s): 黒田明平、松尾侑希子、横須賀章人、三巻祥浩
  • Journal Title: Medical Herb Volume: 27 Pages: 22-25
• [Presentation] 浜防風の化学成分とPPAR-γ活性について (2016)
  • Author(s): 大友佳苗，松尾侑希子，三巻祥浩
  • Organizer: 日本生薬学会 第63回年会
  • Place of Presentation: 富山
  • Year and Date: 2016-09-24
• [Presentation] 浜防風の化学成分と細胞毒性について (2016)
  • Author(s): 小原若菜，松尾侑希子，三巻祥浩
  • Organizer: 日本生薬学会 第63回年会
  • Place of Presentation: 富山
  • Year and Date: 2016-09-24
• [Presentation] ビャクシの化学成分に関する研究 （3） (2016)
  • Author(s): 袴田 遼，山口絵美，松尾侑希子，三巻祥浩
  • Organizer: 日本生薬学会 第63回年会
  • Place of Presentation: 富山
  • Year and Date: 2016-09-24
• [Presentation] ビャクシの化学成分に関する研究 (2) (2016)
  • Author(s): 袴田 遼，山口絵美，松尾侑希子，三巻祥浩
  • Organizer: 日本薬学会 第136年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-27
• [Presentation] ユリ科 Bessera elegans 鱗茎の化学成分と腫瘍細胞毒性 (2014)
  • Author(s): 松尾侑希子, 橋本千聖, 赤城那奈, 三巻祥浩
  • Organizer: 第20回 天然薬物の開発と応用シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2014-11-05 – 2014-11-06
• [Presentation] ビャクシの化学成分に関する研究 （1） (2014)
  • Author(s): 山口絵美，松尾侑希子，三巻祥浩
  • Organizer: 日本生薬学会 第61回年会
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-13 – 2014-09-14
• [Presentation] ビャクダン（Santalum album）の細胞増殖抑制活性成分について (6) (2014)
  • Author(s): 松尾侑希子、三巻祥浩
  • Organizer: 日本薬学会 第134年会
  • Place of Presentation: 熊本