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HIV増殖阻害活性を有する海藻由来生理活性物質の探索

Research Project

Project/Area Number 18J00112
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Aquatic life science
Research InstitutionKumamoto University

Principal Investigator

上野 幹憲  熊本大学, ヒトレトロウイルス学共同研究センター, 特別研究員(PD)

Project Period (FY) 2018-04-25 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsHIV / AIDS / PEL / 海藻 / HIV-1 / アスコフィラン / ポルフィラン / フコイダン / HBV / 多糖類
Outline of Annual Research Achievements

ヒト免疫不全症候群(AIDS)を引き起こす免疫不全ウイルス(HIV)に対する治療薬の開発が行われている。新規の抗HIV薬候補の見出すため,海藻由来生理活性物質の探索を行った。これまでに,海藻由来多糖類はHIVだけでなくヒトB型肝炎ウイルス(HBV)の初期感染を抑制することを見出した。また,エイズ患者では依然として日和見感染が問題となっている。特にヒトヘルペスウイルス-8(HHV-8)/カポジ肉腫関連ウイルス(KSHV)の感染を起因とする原発性滲出性リンパ腫(PEL)に着目した。PELは抗がん剤耐性であり,治療開始後の生存期間は約6か月であり,予後が非常に悪く,他の悪性リンパ腫と比較しても顕著である。加えて,標準的な治療法は依然として確立されていない。よって,PELに有効な化合物の探索を行った。ククルビタシンB(CuB)はキュウリなどのウリ科植物に含まれるステロイド骨格を有する生理活性物質である。植物においては,寄生虫や天敵に対する防御機能を有すると考えられている。これまでに乳がんや肺がんなどに抗がん作用を有すると報告されている。CuBはPEL細胞株に対し,濃度依存的に細胞増殖を抑制した一方で,健常者由来末梢血には毒性を示さないことがわかった。さらに,CuBはG-actinに作用することにより細胞骨格を崩壊させる。その後,アポトーシスを引き起こすことを明らかにした。さらに,高度免疫不全マウス(BRJマウス)を用いたPEL移植モデルマウスの実験では,CuB腹腔内投与により,有意にPEL由来固形腫瘍を抑制することを見出した。よって,CuBはPELの新規の治療薬の候補になりうると考えられた。

Research Progress Status

令和2年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和2年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (20 results)

All 2021 2020 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (13 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Journal Article] Induction of Apoptotic Cell Death in Human Leukemia U937 Cells by C18 Hydroxy Unsaturated Fatty Acid Isolated from Red Alga Tricleocarpa jejuensis2021

    • Author(s)
      Zha Shijiao、Ueno Mikinori、Liang Yan、Okada Seiji、Oda Tatsuya、Ishibashi Fumito
    • Journal Title

      Marine Drugs

      Volume: 19 Issue: 3 Pages: 138-138

    • DOI

      10.3390/md19030138

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Suppressive effects of sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on the production of NO and ROS in LPS-stimulated RAW264.7 cells2021

    • Author(s)
      Liang Yan、Zha Shijiao、Tentaku Masanobu、Okimura Takasi、Jiang Zedong、Ueno Mikinori、Hirasaka Katsuya、Yamaguchi Kenichi、Oda Tatsuya
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 85 Issue: 4 Pages: 882-889

    • DOI

      10.1093/bbb/zbaa115

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cucurbitacin B induces apoptosis of primary effusion lymphoma via disruption of cytoskeletal organization2021

    • Author(s)
      Ueno Mikinori、Kariya Ryusho、Sittithumcharee Gunya、Okada Seiji
    • Journal Title

      Phytomedicine

      Volume: 85 Pages: 153545-153545

    • DOI

      10.1016/j.phymed.2021.153545

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acidic polysaccharides isolated from marine algae inhibit the early step of viral infection2019

    • Author(s)
      Ueno Mikinori、Nogawa Masato、Siddiqui Rokeya、Watashi Koichi、Wakita Takaji、Kato Nobuyuki、Ikeda Masanori、Okimura Takasi、Isaka Shogo、Oda Tatsuya、Ariumi Yasuo
    • Journal Title

      International Journal of Biological Macromolecules

      Volume: 124 Pages: 282-290

    • DOI

      10.1016/j.ijbiomac.2018.11.152

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Increase in anti-inflammatory activities of radical-degraded porphyrans isolated from discolored nori ( Pyropia yezoensis )2018

    • Author(s)
      Yanagido Ayana、Ueno Mikinori、Jiang Zedong、Cho Kichul、Yamaguchi Kenichi、Kim Daekyung、Oda Tatsuya
    • Journal Title

      International Journal of Biological Macromolecules

      Volume: 117 Pages: 78-86

    • DOI

      10.1016/j.ijbiomac.2018.05.146

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HIV-1 Vpr and p21 restrict LINE-1 mobility2018

    • Author(s)
      Kawano Koudai、Doucet Aur?lien J、Ueno Mikinori、Kariya Ryusho、An Wenfeng、Marzetta Flavia、Kuroki Misao、Turelli Priscilla、Sukegawa Sayaka、Okada Seiji、Strebel Klaus、Trono Didier、Ariumi Yasuo
    • Journal Title

      Nucleic Acids Research

      Volume: 46 Issue: 16 Pages: 8454-8470

    • DOI

      10.1093/nar/gky688

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Apolipoprotein E is an HIV-1-inducible inhibitor of viral production and infectivity in macrophages2018

    • Author(s)
      Siddiqui Rokeya、Suzu Shinya、Ueno Mikinori、Nasser Hesham、Koba Ryota、Bhuyan Farzana、Noyori Osamu、Hamidi Sofiane、Sheng Guojun、Yasuda-Inoue Mariko、Hishiki Takayuki、Sukegawa Sayaka、Miyagi Eri、Strebel Klaus、Matsushita Shuzo、Shimotohno Kunitada、Ariumi Yasuo
    • Journal Title

      PLOS Pathogens

      Volume: 14 Issue: 11 Pages: 1007372-1007372

    • DOI

      10.1371/journal.ppat.1007372

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 原発性滲出性リンパ腫に対するククルビタシンBの抗腫瘍効果の検討2020

    • Author(s)
      上野幹憲,刈谷龍昇,シティタンチャリー ガンヤ,岡田誠治
    • Organizer
      第82回日本血液学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Novel midkine inhibitor induces cell cycle arrest and apoptosis in multiple myeloma.2020

    • Author(s)
      Kodcharat Cheevapruk, Mikinori Ueno, Gunya Sittithumcharee, Ryusho Kariya, Somponnat Sampattavanich, Seiji Okada
    • Organizer
      The 82nd Annual Meeting of the Japanese Society of Hematology
    • Related Report
      2020 Annual Research Report
  • [Presentation] Cucurbitacin B induces apoptosis of primary effusion lymphoma via disruption of cytoskeletal organization2020

    • Author(s)
      Ueno M, Kariya R, Sittihumcharee G, Okada S
    • Organizer
      Kickoff Symposium Joint Research Center for Human Retrovirus Infection
    • Related Report
      2019 Annual Research Report
  • [Presentation] 原発性滲出性リンパ腫に対するククルビタシンBの抗腫瘍効果の検討2020

    • Author(s)
      上野幹憲,刈谷龍昇,シティタンチャリーガンヤ,岡田誠治
    • Organizer
      日本農芸化学会2020年度大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ラディカル分解によるスサビノリ由来硫酸化多糖体ポルフィランの低分子化と抗炎症作用増強2018

    • Author(s)
      柳戸彩奈,上野幹憲,山口健一,小田達也
    • Organizer
      平成30年度日本生化学会九州支部例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 海藻由来酸性多糖類の研究からウイルスの研究へ2018

    • Author(s)
      上野幹憲
    • Organizer
      第五回プランクトン学会若手の会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Apolipoprotein E is an HIV-1-inducible inhibitor of viral production and infectivity in macrophages2018

    • Author(s)
      Ariumi Y, Siddiqui R, Ueno M, Nasser H, Koba R, Bhuyan F, Noyori O, Inoue M, Hishiki T, Sukegawa S, Miyagi E, Strebe; K, Matsushita S, Shimotohno S, Suzu S
    • Organizer
      The 66th Annual Meeting of the Japanese Society for Virology
    • Related Report
      2018 Annual Research Report
  • [Presentation] Acidic polysaccharides isolated from marine algae, ascophyllan and fucoidans, inhibit the early step of hepatitis B virus infection2018

    • Author(s)
      Ueno M, Nogawa M, Siddiqui R, Watashi K, Wakita T, Okimura T, Isaka S, Oda T, Ariumi Y
    • Organizer
      The 66th Annual Meeting of the Japanese Society for Virology
    • Related Report
      2018 Annual Research Report
  • [Presentation] Sulfated polysaccharides isolated from marine algae inhibit the early step of hepatitis B virus infection2018

    • Author(s)
      Ueno M, Nogawa M, Siddiqui R, Watashi K, Wakita T, Okimura T, Isaka S, Oda T, Ariumi Y
    • Organizer
      The 19th Kumamoto AIDS Seminar
    • Related Report
      2018 Annual Research Report
  • [Presentation] Apolipoprotein E is an HIV-1-inducible inhibitor of viral production in macrophages2018

    • Author(s)
      Ariumi Y, Siddiqui R, Suzu S, Koba R, Nasser H, Yasuda-Inoue M, Bhuyan F, Noyori O, Ueno M, Hishiki T, Sukegawa S, Miyagi E, Strebel K, Matsushita S, Shimotohno K
    • Organizer
      Retroviruses
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Apolipoprotein E is an HIV-1-inducible inhibitor of viral production and infectivity in macrophages2018

    • Author(s)
      Ariumi Y, Siddiqui R, Ueno M, Nasser H, Koba R, Bhuyan F, Noyori O, Yasuda-Inoue M, Hishiki T, Sukegawa S, Miyagi E, Strebel K, Matsushita S, Shimotohno K, Suzu S
    • Organizer
      Frontiers in Retrovirology Conference 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RNA granule components regulate HBV replication2018

    • Author(s)
      Ariumi Y, Watashi K, Ueno M, Deng L, Hotta H, Wakita T
    • Organizer
      2018 International HBV Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Acidic polysaccharides isolated from marine algae, ascophyllan and fucoidans, inhibit the early step of hepatitis B virus infection2018

    • Author(s)
      Ueno M, Nogawa M, Siddiqui R, Watashi K, Wakita T, Okimura T, Isaka S, Oda T, Ariumi Y
    • Organizer
      2018 International HBV Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2018-05-01   Modified: 2024-03-26  

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