栄養飢餓耐性を解除する天然抗がん剤の探索および細胞内代謝物解析による作用機序解明

2017 Fiscal Year Research-status Report

• Project/Area Number: 16K08319
• Research Institution: University of Toyama
• Principal Investigator: Suresh Awale 富山大学, 和漢医薬学総合研究所, 准教授 (00377243)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: PANC-1 / Antiausterity strategy / pancreatic cancer / Drug Discovery / Natural products / Metabolomics / NMR

Outline of Annual Research Achievements

本課題の目的は、抗緊縮戦略を用いて新規抗膵臓がん剤を見出すこと、またはタンパク質やメタボロームの分析により活性化合物の作用機序を解明することであった。本プロジェクトの2017年度の成果として研究論文11編を査読付き国際学術誌に掲載した。薬用植物Uvaria dac、Chamaecyparis obtusa、Ancistrocladus likoko、Gardenia ternifolia、Calotropis gigantea、またはPropolisにおける活性成分の抗癌活性を詳しく検討した。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

抗緊縮活性を有し選択された化合物の作用機序を検討中である。特に、isopanduratin A及びある新規イソキノリンアルカロイドの作用機序の解明が進められている。また、強力な緊縮活性を有する化合物の源となるタイ薬用植物Citrus hystrix とDerris scandensについて研究中である。

Strategy for Future Research Activity

薬用植物における抗がん化合物の探索を続ける。PI3K/AKT/mTORおよびオートファジーシグナリング経路に特に注目し、選択された抗緊縮化合物の作用機序に関る研究を完了する。さらに、抗緊縮化合物がヒト膵臓がん細胞の代謝に及ぼす影響を継続的に検討する。

Research Products

• [Journal Article] Michellamines A6 and A7, and further mono- and dimeric naphthylisoquinoline alkaloids from a Congolese Ancistrocladus liana and their antiausterity activities against pancreatic cancer cells (2018)
  • Author(s): Lombe B.K., Feineis D., Mudogo V., Brun R., Awale S, Bringmann G.
  • Journal Title: RSC Advances Volume: 8 Pages: 5243-525
  • DOI: 10.1039/C8RA00363G
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A New Alkenylphenol from The Propolis of Stingless Bee Trigona minor (2018)
  • Author(s): Nguyen H.X. , Do T.N.V., Nguyen N.T.T., Dang P.H., Tho L.H., Awale S., Nguyen N.T.T.
  • Journal Title: Natural Products Communication Volume: 13 Pages: 69-70
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ancistrolikokines E-H and Related 5,8'-coupled Naphthylisoquinoline alkaloids from the Congolese Liana Ancistrocladus likoko with Antiausterity Activities against PANC-1 Human Pancreatic Cancer Cells (2017)
  • Author(s): Fayez S. Li J., Feineis D., Mudogo V., Awale S., Bringmann G.
  • Journal Title: RSC Advances Volume: 7 Pages: 53740-53751
  • DOI: DOI:10.1039/C7RA11200A
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Jozilebomines A and B, Naphthylisoquinoline Dimers from the Congolese Liana Ancistrocladus ileboensis, with Antiausterity Activities against the PANC-1 Human Pancreatic Cancer Cell Line (2017)
  • Author(s): Li J., Seupel R., Bruhn T., Feineis D., Kaiser M., Brun R., Mudogo V., Awale S., Bringmann G.
  • Journal Title: J. Nat. Prod. Volume: 80 Pages: 2087-2817
  • DOI: 10.1021/acs.jnatprod.7b00650
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Discovery of potential antiausterity agents from the Japanese Cypress Chamaecyparis obtusa (2017)
  • Author(s): Dibwe D.F., Sun S., Ueda J., Balachandran C., Matsumoto K., Awale S.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 27 Pages: 4898-4903
  • DOI: 10.1016/j.bmcl.2017.09.034
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Chemical Constituents of Propolis from Vietnamese Trigona minor and Their Antiausterity Activity against the PANC-1 Human Pancreatic Cancer Cell Line (2017)
  • Author(s): Nguyen H.X., Nguyen M.T.T., Nguyen N.T., Awale S.
  • Journal Title: . Nat. Prod. Volume: 80 Pages: 2345-2352
  • DOI: 10.1021/acs.jnatprod.7b00375
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Gardenifolins A-H, Scalemic Neolignans from Gardenia ternifolia: Chiral Resolution, Configurational Assignment, and Cytotoxic Activities against the HeLa Cancer Cell Line (2017)
  • Author(s): Tshitenge D.T.,Feineis D., Awale S., Bringmann G.
  • Journal Title: J. Nat. Prod. Volume: 80 Pages: 1604-1614
  • DOI: 10.1021/acs.jnatprod.7b00180
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Lignans from the root of Wikstroemia indica and their cytotoxic activity against PANC-1 human pancreatic cancer cells (2017)
  • Author(s): Chang H., Wang Y., Gao X., Song Z., Awale S., Han N., Liu Z., Yin J.
  • Journal Title: Fitoterapia Volume: 121 Pages: 31-37
  • DOI: 10.1016/j.fitote.2017.06.012
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Phytochemical and cytotoxic studies on the leaves of Calotropis gigantea (2017)
  • Author(s): Nguyen K.D.H., Dang P.H., Nguyen H.X., Nguyen M.T.T., Awale S., Nguyen N.T.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 27 Pages: 2902-2906
  • DOI: 10.1016/j.bmcl.2017.04.087
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Highly oxygenated antiausterity agents from the leaves of Uvaria dac (2017)
  • Author(s): Awale S., Tawila A.M., Dibwe D.F., Ueda J, Sun S., Athikomkulchai S., Balachandran C., Saiki S., Matsumoto K., Esumi H.
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 27 Pages: 1967-1971
  • DOI: 10.1016/j.bmcl.2017.03.021
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] α-Glucosidase Inhibitory and Cytotoxic Taxane Diterpenoids from the Stem Bark of Taxus wallichiana (2017)
  • Author(s): Dang P.H., Nguyen H.X., Duong T.T.T, Tran T.K.T., Nguyen P.T., Vu T.K.T, Vuong H.C, Phan T.H.N, Nguyen M.T.T, Nguyen N.T, Awale S.
  • Journal Title: J. Nat. Prod. Volume: 80 Pages: 1087-1095
  • DOI: 10.1021/acs.jnatprod.7b00006
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Antiausterity activity of isopanduratin-A and its mechanism of action against PANC-1 human pancreatic cancer cells (2018)
  • Author(s): Chandrasekar Balachandran, Dya Fita Dibwe, Suresh Awale
  • Organizer: 日本薬学会第138年会、2018年03月２５日～2018年03月２８日 (金沢)
• [Presentation] Furanocoumarins from the peels of Citrus hystrix and their antiausterity activity against three human pancreatic cancer cell lines (2018)
  • Author(s): Sijia Sun, Dya Fita Dibwe, Chandrasekar Balachandran, Ampai Phrutivorapongkul, Suresh Awale
  • Organizer: 日本薬学会第138年会、2018年03月２５日～2018年03月２８日 (金沢)
• [Presentation] Discovery of potential antiausterity agents from Thai Derris scandens (2018)
  • Author(s): Dya Fita Dibwe, Nusrin Pongterdsak, Kritsaya Chaithatwatthana, Ampai Phrutivorapongkul, Ahmed M. Tawila, Chandrasekar Balachandran, Suresh Awale
  • Organizer: 日本薬学会第138年会、2018年03月２５日～2018年03月２８日 (金沢)
• [Presentation] Application of NMR metabolomics in understanding the physiological target of Kampo medicine (2017)
  • Author(s): Suresh Awale
  • Organizer: 第７回 和漢研・熱研ジョイントセミナー、2017年12月4日（長崎）
• [Presentation] Bergamottin, an anti-austerity agent from Citrus hystrix induced autophagy mediated PANC-1 cell death (2017)
  • Author(s): Sijia Sun, Dya Fita Dibwe, Chandrasekar Balachandran, Ampai Phrutivorapongkul, Suresh Awale
  • Organizer: International Symposium on Scientific Research of Traditional Medicine、2017年11月10 日 （Toyama）
  • Int'l Joint Research
• [Presentation] Study on the anti-austerity activity of Derris scandens extract against the PANC-1 human pancreatic cancer cell line (2017)
  • Author(s): Nusrin Pongterdsak, Kristaya Chaithatwatthana, Ampai Phrutivorapongkul, Sijia Sun, Ahmed M. Tawila, Ashraf M. Omar, Chandrasekar Balachandran, Dya Fita Dibwe, Suresh Awale.
  • Organizer: International Symposium on Scientific Research of Traditional Medicine、2017年11月10 日 （Toyama）
  • Int'l Joint Research
• [Presentation] Anti-austerity activity of Piper betle extract against the PANC-1 human pancreatic cancer cell line (2017)
  • Author(s): Kristaya Chaithatwatthana, Nusrin Pongterdsak, Ampai Phrutivorapongkul, Sijia Sun, Ashraf M. Omar, Ahmed M. Tawila, Chandrasekar Balachandran, Dya Fita Dibwe, Suresh Awale.
  • Organizer: International Symposium on Scientific Research of Traditional Medicine、2017年11月10 日 （Toyama）
  • Int'l Joint Research
• [Presentation] Synthesis and evaluation of preferential cytotoxicity under nutrient-deprived conditions of plumbagin derivatives (2017)
  • Author(s): Takahiro Maruyama, Takahiro Okada, Takuya Okada, Satoyuki Takahara, Chandrashaker Balachandran, Dya Fita Dibwe, Suresh Awale, Naoki Toyooka
  • Organizer: The 35th Medicinal Chemistry Symposium, 201７年03月２５日 ～201７年03月２7日 （Nagoya）
• [Presentation] Discovery of potential anticancer agents from the Japanese cypress “Hinoki” (2017)
  • Author(s): Suresh Awale
  • Organizer: Toyama Academic GALA 2017, 2017年9月27 日 (Toyama).
• [Presentation] Chemical Constituents of Piper longum and their Antiausterity activity (2017)
  • Author(s): Dya Fita Dibwe, Suresh Awale
  • Organizer: Toyama Academic GALA 2017, 2017年9月27 日 (Toyama).
• [Presentation] Discovery of antiausterity strategy based anticancer agents from Citrus hystrix DC. (2017)
  • Author(s): Sijia Sun, Dya Fita Dibwe, Chandrasekar Balachandran, Ampai Phrutivorapongkul, Suresh Awale
  • Organizer: Toyama Academic GALA 2017, 2017年9月27 日 (Toyama).
• [Presentation] Discovery of natural anti-cancer agents targeting cancer cells’ tolerance to nutrition starvation (2017)
  • Author(s): Suresh Awale
  • Organizer: he 1st International Conference on Natural Medicine (ICNM2017), "From Local Wisdom to International Research", 2017年8月5日 ～2017年8月6日 (Bangkok, Thailand)
  • Int'l Joint Research / Invited