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Natural compounds that enhance TRAIL-induced apoptosis : a novel molecular targeted cancer therapy

Research Project

Project/Area Number 18590510
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionNagasaki University

Principal Investigator

HASEGAWA Hiroo  Nagasaki University, 大学院・医歯薬学総合研究科, 助教 (00398166)

Co-Investigator(Kenkyū-buntansha) 山田 恭暉  長崎大学, 大学院・医歯薬学総合研究科, 准教授 (60145232)
上平 憲  長崎大学, 大学院・医歯薬学総合研究科, 教授 (80108290)
小宮山 寛機  北里研究所, 臨床薬理研究所, 部長 (00106676)
林 正彦  いわき明星大学, 薬学科, 教授 (20164965)
Co-Investigator(Renkei-kenkyūsha) 小宮山 寛機  北里大学, 基礎研究所, 所長 (00106676)
林 正彦  いわき明星大学, 薬学科, 教授 (20164965)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2008: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords分子標的治療 / アポトーシス / 成人T細胞白血病・リンパ腫 / 分子標的薬 / TRAIL / 天然由来物質 / 天然物質
Research Abstract

アポトーシス誘導サイトカインTRAILによるアポトーシスを増強する物質を未知の天然物質を含むライブラリーを用いて検索し、特に効果が認められた物質を2種類同定した。ひとつはタイ原産キク科植物Blumea balsamifera由来のフラボノイド(BB1と命名)であり、もうひとつは粘菌由来物質Cycloanthranilylproline-derivative(FCBと命名)であった。いずれの物質も多種の白血病細胞に対しTRAILとの併用による相乗効果を発揮した。相乗効果のメカニズムを詳細に解析し、それぞれに異なるメカニズムであることを解明した。その結果、将来的には抗がん剤として単剤で使用することも可能なポテンシャルと合理性をもつ物質であることがわかった。いずれの成果も定評ある雑誌に掲載された。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (31 results)

All 2008 2007 2006

All Journal Article (26 results) (of which Peer Reviewed: 14 results) Presentation (5 results)

  • [Journal Article] Foxp3 expression on normal and leukemic CD4+CD25+T cells implicated in human T-cell leukemia virus type-1 is inconsistent with Treg cells2008

    • Author(s)
      安部安樹, 鶴田一人, 尾坂明美, 柳原克己, 塚崎邦弘, 長谷川寛雄, 山田恭暉, 上平憲
    • Journal Title

      Eur J Haematol 81(3)

      Pages: 209-17

    • NAID

      120006982421

    • Related Report
      2008 Final Research Report
  • [Journal Article] Characteristic expression of HTLV-1 basic zipper factor (HBZ) transcripts in HTLV-1 provirus-positive cells2008

    • Author(s)
      臼井哲也、柳原克己、塚崎邦弘、村田健、長谷川寛雄, 山田恭暉, 上平憲
    • Journal Title

      Retrovirology 5

      Pages: 34-34

    • NAID

      120006981409

    • Related Report
      2008 Final Research Report
  • [Journal Article] Autocrine and/or paracrine growth of aggressive ATLL cells caused by HGF and c-Met.2008

    • Author(s)
      Onimaru Y
    • Journal Title

      Int J Oncol. 33

      Pages: 697-703

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Screening for genetic heterogeneity in the interferon sensitivity determining region of the hepatitis C virus genome by polymerase chain reaction with melting curve analysis.2008

    • Author(s)
      Sasaki D
    • Journal Title

      Clin Chem Lab Med. 46

      Pages: 966-973

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Usefulness of long-distance inverse polymerase chain reaction for molecular detection of 14q32 translocation in a clinical setting.2008

    • Author(s)
      Ishizaki A
    • Journal Title

      Scand J Clin Lab Invest. 11

      Pages: 1-7

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Foxp3 expression on normal and leukemic CD4+CD25+T cells implicated in human T-cell leukemia virus type-1 is inconsistent with Treg cells.2008

    • Author(s)
      Abe M
    • Journal Title

      Eur J Haematol. 81

      Pages: 209-217

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characteristic expression of HTLV-1 basic zipper factor (HBZ) transcripts in HTLV-1 provirus-positive cells.2008

    • Author(s)
      Usui T
    • Journal Title

      Retrovirology 5

      Pages: 1-11

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum cytochrome c to indicate the extent of ongoing tumor cell death.2008

    • Author(s)
      Osaka A
    • Journal Title

      Int J Lab Hematol. (印刷中)(掲載確定)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel natural compound, a cycloanthranilylproline derivative (Fuligocandin B), sensitizes leukemia cells to apoptosis induced by tumor necrosis factor related apoptosis-inducing ligand (TRAIL) through 15-deoxy-Delta 12, 14 prostaglandin J2 production2007

    • Author(s)
      長谷川寛雄, 山田恭暉, 小宮山寛機, 林正彦, 石橋正巳, 砂塚敏明, 菅原和行, 鶴田一人, 増田昌人, 高須信行, 塚崎邦弘, 朝長万左男, 上平憲
    • Journal Title

      Blood 110(5)

      Pages: 1664-74

    • Related Report
      2008 Final Research Report
  • [Journal Article] High IL-21 receptor expression and apoptosis induction by IL-21 in follicular lymphoma2007

    • Author(s)
      赤松紀彦、山田恭暉、長谷川寛雄、真壁幸樹、浅野竜太郎、熊谷泉、村田健、今泉芳孝、塚崎邦弘、鶴田一人、菅原和行、跡上直、柳原克己、上平憲
    • Journal Title

      Cancer Lett 256(2)

      Pages: 196-206

    • Related Report
      2008 Final Research Report
  • [Journal Article] A novel natural compound, a cycloanthranilylproline derivative (Fuligocandin B), sensitizes leukemia cells to apoptosis induced by tumor necrosis factor related apoptosis-inducing ligand (TRAIL) through 15-deoxy-Delta 12,14 prostaglandin J2 production.2007

    • Author(s)
      H.Hasegawa
    • Journal Title

      blood 100

      Pages: 1664-1674

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of CCR9 in HTLV-1+T cells and ATL cells expressing Tax.2007

    • Author(s)
      D.Nagakubo
    • Journal Title

      Int J Cancer 120

      Pages: 1591-1597

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rapid and high-resolution detection of IgH gene rearrangements using PCR and melting curve analysis.2007

    • Author(s)
      A.Uemura
    • Journal Title

      Int J Lab Hematol. 29

      Pages: 200-207

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High IL-21 receptor expression and apoptosis induction by IL-21 in follicular lymphoma.2007

    • Author(s)
      N.Akamatsu
    • Journal Title

      Cancer Letter 256

      Pages: 196-206

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum cytochrome c to indicate the extent of ongoing tumor cell death.2007

    • Author(s)
      A.Osaka
    • Journal Title

      Int J Lab Hematol. (Epub ahead of print)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Leuconoxine, kopsinitarine, kopsijasmine, and kopsinone derivatives from Kopsia.2007

    • Author(s)
      Lim.SH
    • Journal Title

      J Nat Prod. 70

      Pages: 1380-1383

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biologically active indole alkaloids from Kopsia arborea.J Nat Prod.2007

    • Author(s)
      Lim.KH
    • Journal Title

      J Nat Prod. 70

      Pages: 1302-1307

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biologically active aspidofractinine, rhazinilam, akuammiline, and vincorine alkaloids from Kopsia.2007

    • Author(s)
      Subramaniam G
    • Journal Title

      J Nat Prod. 70

      Pages: 1783-1789

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dihydroflavonol BB-1, an extract of natural plant Blumea balsamifera, abrogates TRAIL resistance in leukemia cells.2006

    • Author(s)
      H.Hasegawa
    • Journal Title

      blood 107(2)

      Pages: 679-688

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Impact of p53 aberration on the progression of Adult T-cell Leukemia/Lymphoma.2006

    • Author(s)
      M.Tawara
    • Journal Title

      Cancer Letter 234(2)

      Pages: 249-255

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel alternative splicing isoform of human T-cell leukemia virus type 1 bZIP factor (HBZ-SI) targets distinct subnuclear localization.2006

    • Author(s)
      K.Murata
    • Journal Title

      Journal of Virology 80(5)

      Pages: 2495-2505

    • Related Report
      2006 Annual Research Report
  • [Journal Article] subtype of aggressive B-cell lymphoma with an unusual presentation of effusion without masses.2006

    • Author(s)
      S.Kamihira
    • Journal Title

      Leukemia and Lymphoma 47(9)

      Pages: 1991-1993

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Survey of chemokine receptor expression reveals frequent co-expression of skin-homing CCR4 and CCR10 in adult T-cell leukemia/lymphoma.2006

    • Author(s)
      H.Harasawa
    • Journal Title

      Leukemia and Lymphoma 47(10)

      Pages: 2163-2173

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Bisindole alkaloids from myxomycetes Arcyria denudata and Arcyria obvelata.2006

    • Author(s)
      K.Kamata
    • Journal Title

      J Nat Prod 69(8)

      Pages: 1252-1254

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Tryptophan 4-aminocinnamamides from a myxomycete Fuligo aurea2006

    • Author(s)
      T.Hosoya
    • Journal Title

      Heterocycles 69

      Pages: 463-468

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Trichiol and 3-epitrichiol acetate, novel cytotoxic sterols with a 2,6-dioxabicyclo[2.2.2]octan-3-one ring system from the myxomycete Trichia favoginea var. persimilis2006

    • Author(s)
      K.Kaniwa
    • Journal Title

      Tetrahedron Letter 47

      Pages: 4351-4354

    • Related Report
      2006 Annual Research Report
  • [Presentation] A novel natural compound, FCB, sensitizes leukemia cells to TRAIL-induced apoptosis through 15-d-PG J2 production2007

    • Author(s)
      長谷川寛雄
    • Organizer
      日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-05
    • Related Report
      2008 Final Research Report
  • [Presentation] A novel natural compound,FCB,sensitizes leukemia cells to TRAIL-induced apoptsis through 15D-PGJ2 production2007

    • Author(s)
      長谷川 寛雄
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-05
    • Related Report
      2007 Annual Research Report
  • [Presentation] A novel natural compound, cycloanthranilylproline derivative (FCB), sensitizes leukemia cells to TRAIL-induced apoptosis through 15-d-PG J2 production2007

    • Author(s)
      長谷川寛雄
    • Organizer
      Annual meeting of International society for Experimental Hematology
    • Place of Presentation
      Hamburg, Germany
    • Year and Date
      2007-09-28
    • Related Report
      2008 Final Research Report
  • [Presentation] A novel natural compound,a cycloanthranilylproline derivative(FCB),sensitizes leukemia cells to TRAIL-induced apoptsis through 15D-PGJ2 production2007

    • Author(s)
      長谷川 寛雄
    • Organizer
      Intemational Society of Experimental Hematology
    • Place of Presentation
      Hamburg,Germany
    • Year and Date
      2007-09-28
    • Related Report
      2007 Annual Research Report
  • [Presentation] Nutlin-3a, an MDM2 antagonist, induces p53-mediated cellular senescence and apoptosis in Adult T-cell Leukemia/Lymphoma cells.2006

    • Author(s)
      長谷川寛雄
    • Organizer
      Annual meeting of American society of hematology
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2006-12-10
    • Related Report
      2008 Final Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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