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Novel small-molecule SIRT1 inhibitors induce cell death in leukaemia cells

Research Project

Project/Area Number 24591413
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionFukuoka University

Principal Investigator

KOZAKO Tomohiro  福岡大学, 薬学部, 准教授 (40398300)

Co-Investigator(Renkei-kenkyūsha) SUZUKI Takayoshi  京都府立医科大学, 医学部, 教授 (90372838)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsATL / HTLV-1 / SIRT1
Outline of Final Research Achievements

Adult T-cell leukaemia/lymphoma (ATL) is an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukaemia virus (HTLV)-1. We previously reported that ATL patients had significantly higher SIRT1 protein levels than healthy controls. Here, we demonstrate that two novel small-molecule SIRT1 inhibitors, NCO-01/04, reduced cell viability and enhanced apoptotic cells in peripheral blood monocyte cells of patients with acute ATL, which has a poor prognosis. Interestingly, NCO-01/04 increased the LC3-II-enriched protein fraction, indicating autophagosome accumulation as well as autophagy. Thus, NCO-01/04 simultaneously caused caspase activation and autophagy. These results suggest that NCO-01/04 is highly effective against ATL cells in caspase-dependent or -independent manners with autophagy, and that its clinical application might improve the prognosis of patients with this fatal disease.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (29 results)

All 2015 2014 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (17 results) Book (3 results) Remarks (1 results)

  • [Journal Article] Shedding by ADAM10 and ADAM17 is associated with progression of adult T-cell leukemia/lymphoma2015

    • Author(s)
      Takemoto S, Kozako T, Pornkuna R.
    • Journal Title

      Integrative Cancer Science and Therapeutics

      Volume: 2 Issue: 1 Pages: 79-81

    • DOI

      10.15761/icst.1000118

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anticancer agents targeted to sirtuins.2014

    • Author(s)
      Kozako T, Suzuki T, Yoshimitsu M, Arima N, Honda S, Soeda S.
    • Journal Title

      Molecules

      Volume: 19 Issue: 12 Pages: 20295-313

    • DOI

      10.3390/molecules191220295

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Assessment of peripheral blood CD4+ adenosine triphosphate activity in patients with rheumatoid arthritis.2013

    • Author(s)
      Akimoto M, Yunoue S, Otsubo H, Yoshitama T, Kodama K, Matsushita K, Suruga Y, Kozako T, Toji S, Hashimoto S, Uozumi K, Matsuda T, Arima N.
    • Journal Title

      Mod Rheumatol.

      Volume: 23 Issue: 1 Pages: 19-27

    • DOI

      10.1007/s10165-012-0621-1

    • NAID

      10031167662

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of exogenous interleukin-7 on CD8(+) T-cell survival and function in human T-cell lymphotropic virus type 1 infection.2013

    • Author(s)
      White Y, Yoshimitsu M, Kozako T, Matsushita K, Koriyama C, Uozumi K, Suzuki S, Kofune H, Arima N.
    • Journal Title

      Leukemia and Lymphoma.

      Volume: 54 Issue: 10 Pages: 2243-2250

    • DOI

      10.3109/10428194.2013.772174

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Liposomes and nanotechnology in drug development: focus on oncotargets2012

    • Author(s)
      Kozako T, Arima N, Yoshimitsu M, Honda S-I, Soeda S
    • Journal Title

      International Journal of Nanomedicine

      Volume: 7 Pages: 4943-4951

    • DOI

      10.2147/ijn.s30726

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] High expression of the longevity gene product SIRT1 and apoptosis induction by sirtinol in adult T-cell leukemia cells2012

    • Author(s)
      Kozako T.
    • Journal Title

      Int J Cancer

      Volume: (In press) Issue: 9 Pages: 2044-2055

    • DOI

      10.1002/ijc.27481

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Vasohibin induces prolyl hydroxylase-mediated degradation of hypoxia-inducible factor-1α in human umbilical vein endothelial cells.2012

    • Author(s)
      Kozako T, Matsumoto N, Kuramoto Y, Sakata A, Motonagare R, Aikawa A, Imoto M, Toda A, Honda S, Shimeno H, Soeda S.
    • Journal Title

      FEBS Lett.

      Volume: 586 Issue: 7 Pages: 1067-1072

    • DOI

      10.1016/j.febslet.2012.03.007

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] LIM-homeo domain transcription factor, Lhx2, is involved in transcriptional control of brain-specific promoter/exon 1f of the2012

    • Author(s)
      Honda, S.-I., Kozako, T., Shimeno, H.
    • Journal Title

      J Neuro

      Volume: 66(2) Issue: 11 Pages: 260-272

    • DOI

      10.1111/j.1365-2826.2012.02356.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Compound C、AICARおよびMetforminによるHTLV-1感染細胞株の増殖抑制効果2014

    • Author(s)
      相川 晃慶、小迫 知弘、横松 恵里佳、 吉満 誠、有馬 直道、坂田 晃、本田 伸一郎、添田 秦司
    • Organizer
      第31回日本薬学会九州支部会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-12-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] アロマターゼの脳特異的プロモーターに存在するシスエレメント、AIIサイトに結合する転写因子の解析2014

    • Author(s)
      山口貴広、本田伸一郎、小迫知弘、相川晃慶、坂田晃、原田信広、添田秦司
    • Organizer
      第31回日本薬学会九州支部会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-12-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脳特異的アロマターゼプロモーターの活性に及すDeaf1のSUMO化の影響2014

    • Author(s)
      本田伸一郎、小迫知弘、相川晃慶、坂田晃、原田信広、添田秦司
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新規SIRT1阻害剤による成人T細胞白血病細胞の増殖抑制効果に関する検討2014

    • Author(s)
      小迫知弘、有馬直道
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新規SIRT1阻害剤による白血病細胞の細胞死に関する検討2014

    • Author(s)
      内田 友一朗、小迫 知弘、鈴木 孝禎、馬島 礼、相川 晃慶、 本田 伸一郎、吉満 誠⁾、有馬 直道、添田 秦司
    • Organizer
      第1回日本HTLV-1学会学術集会
    • Place of Presentation
      東京都
    • Year and Date
      2014-08-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Compound C, AICARおよびMetforminはAMPKを介さずにHTLV-1感染細胞株の増殖抑制作用を示す2014

    • Author(s)
      相川 晃慶、小迫 知弘、横松 恵里佳、 吉満 誠、有馬 直道、坂田 晃、本田 伸一郎、添田 秦司
    • Organizer
      第1回日本HTLV-1学会学術集会
    • Place of Presentation
      東京都
    • Year and Date
      2014-08-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] SIRT1を標的とした成人T細胞白血病治療法に関する検討2014

    • Author(s)
      小迫 知弘、馬島 礼 、鈴木 孝禎、吉満 誠、相川 晃慶、本田 伸一郎、有馬 直道、添田 秦司
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 成人T細胞白血病におけるAMP活性化プロテインキナーゼ標的薬による抗腫瘍効果2014

    • Author(s)
      相川 晃慶、小迫 知弘、横松 恵里佳、吉満 誠、有馬 直道、本田 伸一郎、添田 秦司
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] Deaf1タンパク質の機能ドメインの解析2014

    • Author(s)
      本田 伸一郎,原田 信広、小迫 知弘,相川 晃慶,坂田 晃1,添田 秦司
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 新規SIRT1阻害剤による白血病細胞の増殖抑制効果に関する検討2013

    • Author(s)
      馬島 礼、小迫 知弘、鈴木 孝禎、相川晃慶、本田 伸一郎、吉満 誠、有馬 直道、添田 秦司
    • Organizer
      第6回HTLV-1研究会
    • Place of Presentation
      東京都
    • Related Report
      2013 Research-status Report
  • [Presentation] AMPK活性剤による新規成人T細胞白血病治療法の検討2013

    • Author(s)
      横松 恵里佳、相川晃慶、小迫 知弘、本田 伸一郎、吉満 誠、魚住 公治有馬 直道、添田 秦司
    • Organizer
      第6回HTLV-1研究会(東京都)
    • Place of Presentation
      東京都
    • Related Report
      2013 Research-status Report
  • [Presentation] A novel SIRT1 inhibitor induces apoptosis in leukemic cell lines2013

    • Author(s)
      小迫知弘、有馬直道
    • Organizer
      第72回日本癌学会総会
    • Place of Presentation
      横浜市
    • Related Report
      2013 Research-status Report
  • [Presentation] AMPKを標的とした薬剤を用いた新規成人T細胞白血病治療法の検討2013

    • Author(s)
      相川 晃慶、小迫 知弘、横松 恵里佳、吉満 誠、有馬 直道、本田 伸一郎、添田 秦司
    • Organizer
      第30回日本薬学会九州支部大会
    • Place of Presentation
      佐世保市
    • Related Report
      2013 Research-status Report
  • [Presentation] エネルギー代謝因子を標的とした成人T細胞白血病治療法の検討2012

    • Author(s)
      蒲原裕典、小迫知弘、相川晃慶、吉満誠、有馬直道、田中宏暁、本田伸一郎、添田秦司
    • Organizer
      日本生化学会九州支部例会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Research-status Report
  • [Presentation] エネルギー代謝因子AMPKを標的とした新規成人T細胞白血病治療法の検討2012

    • Author(s)
      相川晃慶、小迫知弘、蒲原裕典、吉満誠、魚住公治、有馬直道、本田伸一郎、添田秦司
    • Organizer
      第5回HTLV-1研究会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] SIRT1活性化剤による白血病細胞の増殖抑制効果に関する検討2012

    • Author(s)
      植村陽菜、小迫知弘、有馬直道、田中宏暁、本田伸一郎、添田秦司
    • Organizer
      第5回HTLV-1研究会
    • Place of Presentation
      東京都
    • Related Report
      2012 Research-status Report
  • [Presentation] アロマターゼの脳特異的発現に関与する転写因子Deaf-12012

    • Author(s)
      本田伸一郎、大下遥子、民本愛、小迫知弘、蔵元佑嘉子,元流梨恵、原田信広、添田秦司
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡市
    • Related Report
      2012 Research-status Report
  • [Book] 薬学生のための病態検査学 改訂第2版2014

    • Author(s)
      編集:三浦 雅一、執筆者:竹橋 正則、丹羽 和紀、高寺 恒雄、松永 俊之、三浦 雅一、小迫 知弘、添田 秦司、木村 聡、佐藤 圭創、古川 勝敏、橋口 照人
    • Total Pages
      264
    • Publisher
      南江堂
    • Related Report
      2014 Annual Research Report
  • [Book] T-Cell Leukemia - Characteristics, Treatment and Prevention2013

    • Author(s)
      Makoto Yoshimitsu, Tomohiro Kozako and Naomichi Arima
    • Total Pages
      307
    • Publisher
      InTech
    • Related Report
      2013 Research-status Report
  • [Book] Major Histocompatibility Complex: Biology, Functions and Roles in Disease2012

    • Author(s)
      Tomohiro Kozako, Shinya Hirata, Makoto Yoshimitsu, and Naomichi Arima
    • Total Pages
      16
    • Publisher
      Nova Science Publishers, Inc.
    • Related Report
      2012 Research-status Report
  • [Remarks] 福岡大学薬学部生化学・病態生化学教室

    • URL

      http://www.pha.fukuoka-u.ac.jp/user/seika/web/

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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