Exploration of bioactive natural products which induce selective apoptosis in tumor cells from Kampo formulas

• Project/Area Number: 23710249
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Living organism molecular science
• Research Institution: Chiba University
• Principal Investigator: TOUME Kazufumi 千葉大学, 大学院・薬学研究院, 助教 (80563981)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 天然物化学 / TRAIL / アポトーシス / 生物活性天然物 / がん / 生薬 / DR5

Research Abstract

In this study, we examined extracts of natural resources including Kampo formulas for bioactive natural products which induce selective apoptosis in tumor cells. As a result of this screening study we have isolated several active compounds. The mode of action for isolated compounds was also investigated.

Research Products

• [Journal Article] β-sitosterol and flavonoids isolated from Bauhinia malabarica found in a screening program for Wnt signal inhibitory activity (2014)
  • Author(s): Park, H.-Y.; Toume, K.; Arai, M. A.; Koyano, T.; Kowithayakorn, T.; Ishibashi, M
  • Journal Title: J. Nat. Med Volume: (in press) Issue: 1 Pages: 242-245
  • DOI: 10.1007/s11418-013-0762-3
  • Peer Reviewed
• [Journal Article] Eudesmane-type Sesquiterpenoid and Guaianolides from Kandelia candel in a Screening Program for Compounds to Overcome TRAIL-resistance (2012)
  • Author(s): Minakawa, T.; Toume, K.; Arai, M. A.; Sadhu, S. K.; Ahmed, F.; Ishibashi, M
  • Journal Title: J. Nat. Prod Volume: 75 Pages: 1431-1435
  • Peer Reviewed
• [Journal Article] Griseoviridin and cyclic hydroxamates found in a screening program for Wnt signal inhibitor (2012)
  • Author(s): Tamai, Y.; Toume, K.; Arai, M. A.; Ishibashi, M
  • Journal Title: Heterocycles Volume: 86 Pages: 1517-1524
  • Peer Reviewed
• [Journal Article] Cycloartane triterpenes and ingol diterpenes isolated from Euphorbia neriifolia in a screening program for death-receptor expression-enhancing activity (2012)
  • Author(s): Toume, K.; Nakazawa, T.; Tahmina, H.; Ohtsuki, T.; Arai, M. A.; Koyano, T.; Kowithayakorn, T.; Ishibashi, M.
  • Journal Title: Planta medica Volume: 78 Pages: 1370-1377
  • Peer Reviewed
• [Journal Article] Katorazone, a novel yellow pigment with2-azaquinone-phenylhydrazone structure produced by Streptomyces sp. IFM 11307 (2012)
  • Author(s): Abdelfattah, M. S.; Toume, K.; Arai, M. A.; Masu, H.; Ishibashi, M.
  • Journal Title: Tetrahedron Lett Volume: 53 Pages: 3346-3348
  • Peer Reviewed
• [Journal Article] Yoropyrazone, a new naphthopyridazone alkaloid isolated from Streptomyces sp. IFM11307 and evaluation of its TRAILresistance-overcoming activity (2012)
  • Author(s): Abdelfattah, M. S.; Toume, K.; Ishibashi, M.
  • Journal Title: J. Antibiot Volume: 65 Pages: 245-248
  • NAID: 10030641514
  • Peer Reviewed
• [Journal Article] Phorbol esters with Wnt signal-augmenting effects isolated from Excoecaria indica (2012)
  • Author(s): Yamaguchi, T.; Toume, K.; Arai, M. A.; Ahmed, F.; Sadhu, S. K.; Ishibashi, M.
  • Journal Title: Nat. Prod. Commun Volume: 7 Pages: 475-477
  • Peer Reviewed
• [Journal Article] Nonactin and related compounds found in a screening program for Wnt signal inhibitory activity (2012)
  • Author(s): Tamai, Y.; Toume, K.; Arai, M. A.; Hayashida, A.; Kato, H.; Shizuri, Y.; Tsukamoto, S.; Ishibashi, M.
  • Journal Title: Heterocycles Volume: 84 Pages: 1245-1250
  • Peer Reviewed
• [Journal Article] Eudesmane-type sesquiterpenoid and guaianolides from Kandelia candel in a screening program for compounds to overcome TRAIL-resistance (2012)
  • Author(s): Minakawa, T.; Toume, K.; Arai, M. A.; Sadhu, S. K.; Ahmed, F.; Ishibashi, M.
  • Journal Title: J. Nat. Prod Volume: 75 Issue: 8 Pages: 1431-1435
  • DOI: 10.1021/np300179c
  • Peer Reviewed
• [Journal Article] Katorazone, a novelyellow pigment with2-azaquinone-phenylhydrazone structure produced by Streptomyces sp. IFM 11299 (2012)
  • Author(s): Abdelfattah, M. S.; Toume, K.; Arai, M. A.; Masu, H.; Ishibashi, M.
  • Journal Title: Tetrahedron Lett Volume: 53 Issue: 26 Pages: 3346-3348
  • DOI: 10.1016/j.tetlet.2012.04.073
  • Peer Reviewed
• [Journal Article] Yoropyrazone, a new naphthopyridazone alkaloid isolated from Streptomyces sp. IFM11307 and evaluation of its TRAILresistance-overcoming activity (2012)
  • Author(s): Abdelfattah, M. S.; Toume, K.; Ishibashi, M.
  • Journal Title: J. Antibiot Volume: 65 Issue: 5 Pages: 245-248
  • DOI: 10.1038/ja.2012.11
  • NAID: 10030641514
  • Peer Reviewed
• [Journal Article] New pyranonaphthoquinones and phenazine alkaloid isolated from Streptomyces sp. IFM 11307 with TRAIL resistance-overcoming activity (2011)
  • Author(s): Abdelfattah, M. S.; Toume, K.; Ishibashi, M.
  • Journal Title: J. Antibiot Volume: 64 Pages: 729-734
  • Peer Reviewed
• [Journal Article] Izumiphenazine D, new phenazoquinoline N-oxide from Streptomyces sp. IFM 11204 (2011)
  • Author(s): Abdelfattah, M. S.; Toume, K.; Ishibashi, M.
  • Journal Title: Chem. Pharm. Bull Volume: 59 Pages: 508-510
  • NAID: 130000648975
  • Peer Reviewed
• [Journal Article] Cycloartane triterpenes isolated from Combretum quadrangulare in a screening program for death-receptor expression enhancing activity (2011)
  • Author(s): Toume, K.; Nakazawa, T.; Ohtsuki, T.; Arai, M. A.; Koyano, T.; Kowithayakorn, T.; Ishibashi, M.
  • Journal Title: J. Nat. Prod Volume: 74 Pages: 249-255
  • Peer Reviewed
• [Journal Article] Isolation and structure elucidation of izuminosides A-C: a rare phenazine glycosides from Streptomyces sp. IFM11260 (2011)
  • Author(s): Abdelfattah, M. S.; Toume, K.; Ishibashi, M.
  • Journal Title: J. Antibiot Volume: 64 Pages: 271-275
  • NAID: 10030638410
  • Peer Reviewed
• [Journal Article] Tubiferic acid, a new 9,10-secocycloartane triterpenoid acid isolated from the myxomycete Tubulifera arachnoidea (2011)
  • Author(s): Ippongi, Y.; Ohtsuki, T.; Toume, K.; Arai, M.A.; Yamamoto, Y.; Ishibashi, M.
  • Journal Title: Chem. Pharm. Bull Volume: 59 Pages: 279-281
  • NAID: 130000405528
  • Peer Reviewed
• [Journal Article] 2-Methoxy-1,4-naphthoquinone isolated from Impatiens balsamina in a screening program for activity to inhibit Wnt signaling (2011)
  • Author(s): Mori, N.; Toume, K.; Arai, M. A.; Koyano, T.; Kowithayakorn, T.; Ishibashi, M.
  • Journal Title: J. Nat. Med Volume: 65 Pages: 234-236
  • NAID: 10029460988
  • Peer Reviewed
• [Journal Article] Cryptolepine, isolated from Sida acuta, sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis (2011)
  • Author(s): Ahmed, F.; Toume, K.; Ohtsuki, T.; Rahman, M.; Sadhu, S. K.; Ishibashi, M.
  • Journal Title: Phytotherapy Research Volume: 25 Pages: 147-150
  • Peer Reviewed
• [Journal Article] New pyranonaphthoquinones and phenazine alkaloid isolated from Streptomyces sp. IFM11307 with TRAIL resistance-overcoming activity (2011)
  • Author(s): Abdelfattah, M. S.; Toume, K.; Ishibashi, M.
  • Journal Title: J. Antibiot Volume: 64 Issue: 11 Pages: 729-734
  • DOI: 10.1038/ja.2011.85
  • NAID: 10030640679
  • Peer Reviewed
• [Journal Article] Cycloartane Triterpenes Isolated from Combretum quadrangulare in a Screening Program for Death-Receptor Expression Enhancing Activity (2011)
  • Author(s): Toume, K.; Nakazawa,T.; Ohtsuki, T.; Arai, M.A.; Koyano, T.; Kowithayakorn, T.; Ishibashi, M.
  • Journal Title: J.Nat.Prod. Volume: 74 Issue: 2 Pages: 249-255
  • DOI: 10.1021/np100784t
  • Peer Reviewed
• [Journal Article] Isolation and structure elucidation of izuminosides A-C: a rare phenazine glycosides from Streptomyces sp. IFM 11260 (2011)
  • Author(s): Abdelfattah, M. S.; Toume, K.; Ishibashi, M.
  • Journal Title: J. Antibiot. Volume: 64 Pages: 271-275
  • NAID: 10030638410
  • Peer Reviewed
• [Presentation] Calotropis gigantea からの Wnt シグナル阻害作用をもつカ ルデノリド (2012)
  • Author(s): 朴賢英, 當銘 一文 ,荒井緑,S. K. Sadhu, F. Ahmed,石橋正己
  • Organizer: 第19回天然薬物の開発と応用シンポジウム講演要旨集
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-02
• [Presentation] Xylocarpus granatum からの Wnt シグナル阻害作用 をもつ天然化化合物の探索 (2012)
  • Author(s): 神谷謙太朗, 當 銘 一 文 ,荒井緑,S. K.Sadhu,F. Ahmed,石橋正己
  • Organizer: 第19回天 然薬物の開発と応用シンポジウム講演 要旨集 85-87
  • Place of Presentation: 大阪
  • Year and Date: 2012-11-02
• [Presentation] TRAIL耐性克服作用をもつ天然物の探索 : Artocarpus champeden のプレニルフラボン成分 (2012)
  • Author(s): 皆川朋皓, 當 銘一文 ,荒井緑,小谷野喬, T. Kowithayakorn,石橋正己
  • Organizer: 第56回香料・テルペンおよび精油化学に関する討論会講演要旨集
  • Place of Presentation: 鹿児島
  • Year and Date: 2012-10-28
• [Presentation] 千葉産放線菌由来新規生物活性芳香族複素環化合物 (2012)
  • Author(s): M.Abdelfattah,當銘一文,荒井緑,石橋正己
  • Organizer: 第54回天然有機化合物討論会講演要旨集
  • Place of Presentation: 東京
  • Year and Date: 2012-09-18
• [Presentation] 細胞 毒性を有する放線菌由来マクロラクタム (2012)
  • Author(s): 塚原健太郎,當銘一文,石橋正己
  • Organizer: 日本生薬学会第59年会講演要旨集
  • Place of Presentation: 千葉
  • Year and Date: 2012-09-18
• [Presentation] Xylocarpus granatum 由来の Wnt シグナル阻害作用をもつ新規リモノイド (2012)
  • Author(s): 神谷謙太朗, 當銘一文,荒井緑,S. K.Sadhu,F. Ahmed,石橋正己
  • Organizer: 日本生薬学会第59年会講演要旨集
  • Place of Presentation: 千葉
  • Year and Date: 2012-09-18
• [Presentation] Search for bioactive natural products from Curcuma comosa with Wnt signal inhibitory activity (2012)
  • Author(s): R. G. Fuentes,當銘一文,荒井緑,小谷野喬,T. Kowithayakorn,石橋正己
  • Organizer: 日本生薬学会第59年会講演要旨集
  • Place of Presentation: 千葉
  • Year and Date: 2012-09-18
• [Presentation] Calotropis gigantea 由来の Wnt シグナル阻害するカルデノライド (2012)
  • Author(s): 朴賢英, 當銘一文 ,荒井緑,S. K. Sadhu, F. Ahmed,石橋正己
  • Organizer: 日本生薬学会第59年会講演要旨集
  • Place of Presentation: 千葉
  • Year and Date: 2012-09-18
• [Presentation] Artocarpus communis 等からのTRAIL 耐性克服作用を有する天然物の探索 (2012)
  • Author(s): 土生理, 當 銘 一文 ,荒井緑,小谷野喬, T. Kowithayakorn,S. K. Sadhu,F. Ahmed, 石橋正己
  • Organizer: 日本生薬学会第59年会講演要旨集
  • Place of Presentation: 千葉
  • Year and Date: 2012-09-17
• [Presentation] "疾患および再生シグナルに作用する天然物の探索", 新学術領域研究「天然物ケミカルバイオロジー～分子標的と活性制御～」 (2012)
  • Author(s): 石橋正己,荒井緑,當銘一文
  • Organizer: 第2回公開シンポジウム講演要旨集17-18
  • Place of Presentation: 東京
  • Year and Date: 2012-06-18
• [Presentation] Wnt シグナル阻害作用をもつ Xylocarpus granatum 由 来の新規リモノイド (2012)
  • Author(s): 神谷謙太朗,當銘一文,S. K. Sadhu,F.Ahmed,荒井緑,石橋正己
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] Streptomyces sp. IFM11307ら単離した TRAIL 耐性克服作用をもつグリセウシン類エナンチオマー (2012)
  • Author(s): M. Abdelfattah, 當銘一文 ,石橋正己
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] Artocarpus champeden からの TRAIL 耐性克服作用を 有する天然物の探索 (2012)
  • Author(s): 皆川朋皓, 當銘一文 ,荒井緑,小谷野喬, T. Kowithayakorn,石橋正己
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] Artocarpus communis からの TRAIL 耐性克服作用を有する天然物の探索 (2012)
  • Author(s): 土生理,當銘一文,荒井緑,小谷野喬,T. Kowithayakorn,石橋正己
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] Derris indica等からのデス受容体誘導作用をもつ天然物の探索 (2012)
  • Author(s): T. Hoque, 當銘一文 ,荒井緑,S. K. Sadhu,F. Ahmed,石橋正己
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] 海洋 放線菌から単離した TRAIL 耐性克服作 用をもつクロモマイシン類 (2012)
  • Author(s): 塚原健太郎,當銘一文,石橋正己
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-30
• [Presentation] Calotropis gigantea からの Wnt シグナル阻害作用をもつ天然物 の 探 索 (2012)
  • Author(s): 朴賢英,當銘一文,荒井緑,S. K. Sadhu, F. Ahmed,石橋正己
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-29
• [Presentation] Cardenolides Isolated from Calotropis gigantea with WntSignaling Inhibitory Activity (2012)
  • Author(s): 朴賢英, 當銘一文 ,荒井緑,S. K. Sadhu, F. Ahmed ,石橋正己
  • Organizer: The 7th KSP-JSP-CCTCNM Joint Symposium on Pharmacognosy
  • Place of Presentation: Seoul, Korea
• [Presentation] Streptomyces sp. IFM11307から単離したTRAIL耐性克服作用をもつグリセウシン類エナンチオマー (2012)
  • Author(s): M. Abdelfattah，當銘一文，石橋正己
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] Artocarpus champedenからのTRAIL耐性克服作用を有する天然物の探索 (2012)
  • Author(s): 皆川朋皓，當銘一文，荒井緑，小谷野喬，T. Kowithayakorn，石橋正己
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] Artocarpus communisからのTRAIL耐性克服作用を有する天然物の探索 (2012)
  • Author(s): 土生理，當銘一文，荒井緑，小谷野喬，T. Kowithayakorn，石橋正己
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
• [Presentation] ピロン環およびビスインドール骨格を含む変形菌の化学成分 (2011)
  • Author(s): 石橋正己,新谷彰教, 當銘一文 ,荒井緑
  • Organizer: 第41回複素環化学討論会講演要旨集
  • Place of Presentation: 熊本
  • Year and Date: 2011-10-25
• [Presentation] Kandelia candel からの TRAIL 耐性克服作用を有する天 然物の探索 (2011)
  • Author(s): 皆川朋皓, 當銘一文 ,荒井緑,S. K. Sadhu, F. Ahmed,石橋正己
  • Organizer: 日本生薬学会第58年会講演要旨集
  • Place of Presentation: 東京
  • Year and Date: 2011-09-28
• [Presentation] Xylocarpus granatum からのWntシグナル阻害作用をもつ天然物の探索 (2011)
  • Author(s): 神谷謙太朗,森直美, 當銘一文 ,荒井緑, S. K. Sadhu , F. Ahmed , 石橋 正己
  • Organizer: 日本生薬学会第58年会講演要旨集
  • Place of Presentation: 東京
  • Year and Date: 2011-09-28
• [Presentation] Search for bioactive constituents from Derris indica with DR5 promoter activity (2011)
  • Author(s): Hoque Tahmina, 當銘一文 ,荒井緑,S. K.Sadhu,F. Ahmed,石橋正己
  • Organizer: 日本生薬学会第58年会講演要旨集
  • Place of Presentation: 東京
  • Year and Date: 2011-09-27
• [Presentation] Calotropis gigantea からのWntシグナル阻害作用をもつ天 然物の探索 (2011)
  • Author(s): 朴賢英, 當銘一文 ,荒井緑,S. K. Sadhu, F. Ahmed,石橋正己
  • Organizer: 日本生薬学会第58年会講演要旨集
  • Place of Presentation: 東京
  • Year and Date: 2011-09-27
• [Presentation] 放線菌からの Wnt シグナル阻害作用をもつ天然物の探索 (2011)
  • Author(s): 玉井佑弥, 當銘一文 ,荒井緑,石橋正己
  • Organizer: 日本生薬学会第58年会講演要旨集
  • Place of Presentation: 東京
  • Year and Date: 2011-09-27
• [Presentation] ウィントシグナルを制御する天然物の探索 (2011)
  • Author(s): 當銘一文,荒井緑,石橋正己
  • Organizer: 日本生薬学会第58年会講演要旨集
  • Place of Presentation: 東京
  • Year and Date: 2011-09-27
• [Presentation] Kandelia candelからのTRAIL 耐性克服作用を有する天然物の探索 (2011)
  • Author(s): 皆川朋皓，當銘一文，荒井緑，S. K. Sadhu，F. Ahmed，石橋正己
  • Organizer: 日本生薬学会第58年会
  • Place of Presentation: 東京
• [Presentation] Search for bioactive constituents from Derris indica with DR5 promoter activity (2011)
  • Author(s): Hoque Tahmina，當銘一文，荒井緑，S. K. Sadhu，F. Ahmed，石橋正己
  • Organizer: 日本生薬学会第58年会
  • Place of Presentation: 東京
• [Presentation] ウィントシグナルを制御する天然物の探索 (2011)
  • Author(s): 當銘一文，荒井緑，石橋正己
  • Organizer: 日本生薬学会第58年会(招待講演)
  • Place of Presentation: 東京
• [Presentation] Saussurea hypoleucaからのTRAIL耐性克服作用を有する天然物の探索
  • Author(s): 土生理，當銘一文，荒井緑，S. K. Sadhu，F. Ahmed，石橋正己
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
• [Presentation] Calotropis giganteaからのWntシグナル阻害作用をもつカルデノリド
  • Author(s): 朴賢英，當銘一文，荒井緑，S. K. Sadhu，F. Ahmed，石橋正己
  • Organizer: 第19回天然薬物の開発と応用シンポジウム
  • Place of Presentation: 大阪
• [Presentation] TRAIL耐性克服作用をもつ天然物の探索：Artocarpus champedenのプレニルフラボン成分
  • Author(s): 皆川朋皓，當銘一文，荒井緑，小谷野喬，T. Kowithayakorn，石橋正己
  • Organizer: 第56回香料・テルペンおよび精油化学に関する討論会
  • Place of Presentation: 鹿児島
• [Presentation] 千葉産放線菌由来新規生物活性芳香族複素環化合物
  • Author(s): M. Abdelfattah，當銘一文，荒井緑，石橋正己
  • Organizer: 第54回天然有機化合物討論会
  • Place of Presentation: 東京
• [Presentation] Xylocarpus granatum由来のWntシグナル阻害作用をもつ新規リモノイド
  • Author(s): 神谷謙太朗，當銘一文，荒井緑，S. K. Sadhu，F. Ahmed，石橋正己
  • Organizer: 日本生薬学会第59年会
  • Place of Presentation: 千葉
• [Remarks] 活性構造化学研究室
  • URL: http://www.p.chiba-u.ac.jp/lab/kouzou/
• [Remarks]
  • URL: http://www.p.chiba-u.ac.jp/lab/kouzou/
• [Patent(Industrial Property Rights)] エルモニン (2013)
  • Inventor(s): 石橋正己・塚原健太郎・當銘一文
  • Industrial Property Rights Holder: 千葉大学
  • Industrial Property Number: 2013-068062
  • Filing Date: 2013-03-28