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Elucidation of molecular mechanism for chemoresistance elicited by lipid peroxide-detoxifying enzymes.

Research Project

Project/Area Number 22790074
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionGifu Pharmaceutical University

Principal Investigator

MATSUNAGA Toshiyuki  岐阜薬科大学, 薬学部, 准教授 (80306274)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords癌 / 還元酵素 / 抗癌剤 / 過酸化脂質
Research Abstract

Up-regulation of aldo-keto reductase (AKR) 1B10 was provoked with resistance development of human colon cancer HT29 cells toward doxorubicin or mitomycin C. In addition, results in several experiments with the two resistant cancer cellssuggest that the high AKR1B10 expression contributes tomechanism(s) of the chemoresistance through facilitating the reductase activity toward the drugs and antioxidant activity. Furthermore, overexpression and inhibition of the enzyme in the non-resistant cells decreased and increased, respectively, susceptibility to cytotoxic effects of the drugs, raising the possibility that AKR1B10 is a predominant factor involved in gain of colon cancer chemoresistance.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (39 results)

All 2013 2012 2011 2010 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results) Presentation (22 results) Remarks (4 results)

  • [Journal Article] Modulation of activity and inhibitor sensitivity of rabbit aldose reductase-like protein (AKR1B19) by oxidized glutathione and SH-reagents2013

    • Author(s)
      Satoshi Endo
    • Journal Title

      Chemico-Biological Interactions

      Volume: 202 Issue: 1-3 Pages: 146-152

    • DOI

      10.1016/j.cbi.2012.11.026

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers2012

    • Author(s)
      Matsunaga T, Hojo A, Yamane Y, Endo S, El-Kabbani O, Hara A
    • Journal Title

      Chem. Biol. Interact

      Volume: 202 Issue: 1-3 Pages: 234-242

    • DOI

      10.1016/j.cbi.2012.09.024

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Human Aldose Reductase-Like Protein (AKR1B10) by α- and γ-Mangostins, Major Components of Pericarps of Mangosteen2012

    • Author(s)
      Soda M, Endo S
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 35 Issue: 11 Pages: 2075-2080

    • DOI

      10.1248/bpb.b12-00538

    • NAID

      130001872266

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of rabbit aldose reductase-like protein with 3b-hydroxysteroid dehydrogenase activity2012

    • Author(s)
      Satoshi Endo
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 527 Issue: 1 Pages: 23-30

    • DOI

      10.1016/j.abb.2012.07.012

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Selective inhibition of human type-5 17β-hydroxysteroid dehydrogenase(AKR1C3) by bacchari n, a component of brazilian propolis2012

    • Author(s)
      Satoshi Endo, Toshiyuki Matsunaga, Ayano Kanamori, Youko Otsuji, Hirok o Nagai, Krithika Sundaram, Ossama El-Kabbani, Naoki Toyooka, Shozo O hta and A kira
    • Journal Title

      J. Nat. Prod.

      Volume: 75 Issue: 4 Pages: 716-721

    • DOI

      10.1021/np201002x

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structure ofthe His269Arg mutant of the rat aldose reductase-like protein AKR1B14 complexed with NADPH2012

    • Author(s)
      Sundaram K、Endo S、Matsunaga T、Tanaka N、Hara A、El-Kabbani O
    • Journal Title

      Acta.Crystallogr.Sect.F Struct.Biol.Cryst.Commun.

      Volume: 68巻 Issue: 4 Pages: 400-403

    • DOI

      10.1107/s1744309112008810

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reduction of cytotoxic p-quinone metabolites of tert-butylhydroquinone by human aldo-keto reductase (AKR) 1B102012

    • Author(s)
      Matsunaga T、Endo S、Takemura M、Soda M、Yamamura K、Tajima K、Miura T、Terada T、El-Kabbani O、Hara A
    • Journal Title

      Drug Metab. Pharmacokinet

      Volume: 27巻 Pages: 553-558

    • NAID

      130004463280

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aldo-keto reductase 1B10 and its role in proliferation capacity of drug-resistant cancers2012

    • Author(s)
      Matsunaga T, Wada Y, Endo S, Soda M, El-Kabbani O, Hara A
    • Journal Title

      Front. Pharmacol

      Volume: 3 Pages: 5-11

    • DOI

      10.3389/fphar.2012.00005

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design, syn thesis and evaluation of caffeic ac id phenethyl ester-based inhibitors targeting a selectivity pocket in the active site of human aldo-keto reductase 1B102012

    • Author(s)
      Midori Soda, Dawei Hu, Satoshi Endo, Mayuko Takemura, Jie Li, Ryogo Wa da, Syohei Ifuku, Hai-Tao Zhao, Oss ama El-Kabbani, Shozo Ohta, Keiko Y amamura, Naoki Toyooka, Akira Hara, and Toshiyuki Matsunaga
    • Journal Title

      Eur. J. Med. Chem.

      Volume: 48 Pages: 321-329

    • DOI

      10.1016/j.ejmech.2011.12.034

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduction of Cytotoxic <i>p</i>-Quinone Metabolites of <i>tert</i>-Butylhydroquinone by Human Aldo-keto Reductase (AKR) 1B102012

    • Author(s)
      Matsunaga T.
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 27 Issue: 5 Pages: 553-558

    • DOI

      10.2133/dmpk.DMPK-12-NT-012

    • NAID

      130004463280

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sele ctive Inhibition of the Tumor Marker Aldo-keto Reductase Family Member 1B1 0 by Oleanolic Acid2011

    • Author(s)
      Mayuko Takemura, Satoshi Endo, Toshiy uki Matsunaga, Midori Soda, Hai-Tao Zhao, Ossama El-Kabbani, Kazuo Tajima, Munekazu Iimuma, and Akira Hara
    • Journal Title

      J. Nat. Prod.

      Volume: 74 Issue: 5 Pages: 1201-1206

    • DOI

      10.1021/np200118q

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of the aldo-keto reductase, AKR1B10, in mitomycin-c resistance through reactive oxygen speciesdependent mechanisms2011

    • Author(s)
      Matsunaga T, Yamane Y
    • Journal Title

      Anticancer Drugs

      Volume: 22 Issue: 5 Pages: 402-408

    • DOI

      10.1097/cad.0b013e3283448df0

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of rat and human aldo-k eto reductases in metabolism of farne sol and geranylgeraniol2011

    • Author(s)
      Satoshi Endo, Toshiyuki Matsunaga, Ch isato Ohta, Midori Soda, Ayano Kanam ori, Yukio Kitade, Satoshi Ohno, Kaz uo Tajima, Ossama El-Kabbani and Akir a Hara
    • Journal Title

      Chem. Biol. Interact.

      Volume: 191 Issue: 1-3 Pages: 261-268

    • DOI

      10.1016/j.cbi.2010.12.017

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] 肺癌細胞のシスプラチン耐性に対するアルドケト還元酵素1B10阻害剤の有用性2012

    • Author(s)
      友國琢允、松永俊之、北條杏季、森川嘉文、遠藤智史、原明
    • Organizer
      平成24年度日本薬学会東海支部例会
    • Place of Presentation
      岐阜
    • Year and Date
      2012-11-18
    • Related Report
      2012 Final Research Report
  • [Presentation] ブチルヒドロキシアニソールのキノン代謝物によるオートファジー細胞死の誘導2012

    • Author(s)
      西山彩子、遠藤智史、曽田翠、竹村麻祐子、藤本愛理、松永俊之、田島和男、原明
    • Organizer
      平成24年度日本薬学会東海支部例会
    • Place of Presentation
      岐阜
    • Year and Date
      2012-11-18
    • Related Report
      2012 Final Research Report
  • [Presentation] プロポリス成分baccharinによる前立腺・乳癌治療の創薬標的AKR1C3の選択的阻害2012

    • Author(s)
      大辻陽子、永井寛子、金森綾野、遠藤智史、松永俊之、原明
    • Organizer
      第76回日本生化学会中部支部例会
    • Place of Presentation
      岡崎
    • Year and Date
      2012-05-26
    • Related Report
      2012 Final Research Report
  • [Presentation] 大腸癌細胞のシスプラチン耐性獲得におけるアルドケト還元酵素の高発現の意義2012

    • Author(s)
      北條杏季、松永俊之、山根有未、森田宏美、山口綾乃、遠藤智史、原明
    • Organizer
      第76回日本生化学会中部支部例会
    • Place of Presentation
      岡崎
    • Year and Date
      2012-05-26
    • Related Report
      2012 Final Research Report
  • [Presentation] ウサギのアルドース還元酵素類似タンパクは3β-ヒドロキシステロイド脱水素酵素活性を示す2012

    • Author(s)
      熊田翔、藤本愛理、遠藤智史、松永俊之、原明、田島和男、真野純一
    • Organizer
      第76回日本生化学会中部支部例会
    • Place of Presentation
      岡崎
    • Year and Date
      2012-05-26
    • Related Report
      2012 Final Research Report
  • [Presentation] Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers2012

    • Author(s)
      MatsunagaT、HojoA、YamaneY、EndoS、El-KabbaniO、HaraA
    • Organizer
      16th International Symposium of Enzymology and Molecular Biology of Carbonyl Metabolism
    • Place of Presentation
      ドイツ
    • Related Report
      2012 Final Research Report
  • [Presentation] Modulation of activity and inhibitor sensitivity of rabbit aldose reductase-like protein by oxidized glutathione and SH-reagents2012

    • Author(s)
      EndoS、KumadaS、FujimotoA、MatsunagaT、OhnoS、ManoJ、TajimaK、El-Ka bbaniO、HaraA
    • Organizer
      16th International Symposium of Enzymology and Molecular Biology of Carbonyl Metabolism
    • Place of Presentation
      ドイツ
    • Related Report
      2012 Final Research Report
  • [Presentation] Pathophysiological roles of aldo-keto reductases (AKR1C1 and AKR1C3) in development of cisplatin resistance in human colon cancers.2012

    • Author(s)
      Matsunaga T.
    • Organizer
      16th International Symposium of Enzymology and Molecular Biology of Carbonyl Metabolism
    • Place of Presentation
      Germany
    • Related Report
      2012 Annual Research Report
  • [Presentation] Modulation of activity and inhibitor sensitivity of rabbit aldose reductase-like protein by oxidized glutathione and SH-reagents.2012

    • Author(s)
      Endo S.
    • Organizer
      16th International Symposium of Enzymology and Molecular Biology of Carbonyl Metabolism
    • Place of Presentation
      Germany
    • Related Report
      2012 Annual Research Report
  • [Presentation] 大腸癌細胞のオキサリプラチン耐性におけるカルボニル還元酵素の意義2011

    • Author(s)
      飯田桂子、松永俊之、和田康弘、北條杏季、遠藤智史、原明
    • Organizer
      平成23年度日本薬学会東海支部例会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-11-23
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] Design, synthesis and evaluation of caffeic acid phenethyl ester-based inhibitors targeting a selectivity pocket in the active site of human aldo-keto reductase (AKR) 1B102011

    • Author(s)
      EndoS、MatsunagaT、SodaM、TakemuraM、HuD、LiJ、WadaR、IfukuS、ToyookaN、ZhaoHT、El-KabbaniO
    • Organizer
      8th AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] 選択的AKR1B10阻害に基づく新規抗がん剤の開発研究(2)2011

    • Author(s)
      胡大イ、李杰、松谷裕二、杉本健士、遠藤智史、松永俊之、原明、El-Kabbani O、豊岡尚樹
    • Organizer
      平成23年度有機合成化学北陸セミナー
    • Place of Presentation
      坂井
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] 選択的AKR1B10阻害に基づく新規抗がん剤の開発研究(1)2011

    • Author(s)
      胡大イ、李杰、和田亮吾、伊福翔平、曽田翠、竹村麻祐子、遠藤智史、松永俊之、原明、ZhaoHT、El-KabbaniO、豊岡尚樹
    • Organizer
      平成23年度有機合成化学北陸セミナー
    • Place of Presentation
      坂井
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] オキザリプラチン耐性大腸癌細胞におけるアルドケト還元酵素1B10発現と増殖能の関連性2011

    • Author(s)
      和田康弘、松永俊之、飯田桂子、友國琢允、北條杏季、遠藤智史、坂野喜子、原明
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2012 Final Research Report 2011 Annual Research Report
  • [Presentation] Design, synthesis and evaluation of caffeic acid phenethyl ester-based inhibitors targeting a selectivity pocket in the active site of human aldo-keto reductase (AKR) 1B102011

    • Author(s)
      Satoshi Endo, ら
    • Organizer
      8th AFMC international medicinal chemistry symposium
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report
  • [Presentation] マイトマイシンC耐性大腸癌細胞におけるアルドケト還元酵素1B10の発現量の増加2010

    • Author(s)
      山根有未、松永俊之、飯田桂子、遠藤智史、原明
    • Organizer
      第33回日本分子生物学会年会第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-10
    • Related Report
      2012 Final Research Report
  • [Presentation] マイトマイシンC耐性大腸癌細胞におけるアルドケト還元酵素1B10の発現量の増加2010

    • Author(s)
      山根有未、松永俊之、飯田桂子、遠藤智史、原明
    • Organizer
      第33回日本分子生物学会年会 第83回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] ウサギのアルドース還元酵素類似タンパクは3β-ヒドロキシステロイド脱水素酵素活性を示す.

    • Author(s)
      熊田 翔
    • Organizer
      第76回日本生化学会中部支部例会
    • Place of Presentation
      岡崎
    • Related Report
      2012 Annual Research Report
  • [Presentation] プロポリス成分baccharinによる前立腺・乳癌治療の創薬標的AKR1C3の選択的阻害.

    • Author(s)
      大辻 陽子
    • Organizer
      第76回日本生化学会中部支部例会
    • Place of Presentation
      岡崎
    • Related Report
      2012 Annual Research Report
  • [Presentation] 大腸癌細胞のシスプラチン耐性獲得におけるアルドケト還元酵素の高発現の意義.

    • Author(s)
      北條 杏季
    • Organizer
      第76回日本生化学会中部支部例会
    • Place of Presentation
      岡崎
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肺癌細胞のシスプラチン耐性に対するアルドケト還元酵素1B10阻害剤の有用性.

    • Author(s)
      友國 琢允
    • Organizer
      平成24年度日本薬学会東海支部例会
    • Place of Presentation
      岐阜
    • Related Report
      2012 Annual Research Report
  • [Presentation] ブチルヒドロキシアニソールのキノン代謝物によるオートファジー細胞死の誘導.

    • Author(s)
      西山 彩子
    • Organizer
      平成24年度日本薬学会東海支部例会
    • Place of Presentation
      岐阜
    • Related Report
      2012 Annual Research Report
  • [Remarks] 岐阜薬科大学生化学研究室ホームページ

    • URL

      http://www.gifu-pu.ac.jp/lab/seika/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 岐阜薬科大学 生化学研究室 ホームページ

    • URL

      http://www.gifu-pu.ac.jp/lab/seika/index.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.gifu-pu.ac.jp/lab/seika/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.gifu-pu.ac.jp/lab/seika/index.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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