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Identification and characterization of phytochemical-targeted genes using a genome wide yeast screening system

Research Project

Project/Area Number 17H03818
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Food science
Research InstitutionOkayama University

Principal Investigator

Nakamura Yoshimasa  岡山大学, 環境生命科学研究科, 教授 (60324381)

Co-Investigator(Kenkyū-buntansha) 佐藤 あやの  岡山大学, ヘルスシステム統合科学研究科, 准教授 (40303002)
守屋 央朗  岡山大学, 異分野融合先端研究コア, 准教授 (60500808)
中村 俊之  岡山大学, 環境生命科学研究科, 助教 (90706988)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Keywords食品 / 出芽酵母 / 分子生物学 / 遺伝子 / 生化学 / イソチオシアネート / 求電子性
Outline of Final Research Achievements

We identified 12 resistance genes against benzyl isothiocyanate (BITC) from total 6000 yeast genes using a new evaluation model system, the budding yeast gene tug-of-war method (gTOW method). A human cancer cell line stably overexpressing the human homologue (Mis12) of BITC resistance gene MTW1 was established, which showed high resistance to BITC. Mis12 knockdown conversely increased sensitivity. It was also suggested that the expression of Mis12 is down-regulated by BITC via post-translational modification, which contributes to suppressive effect of BITC on colon cancer cell proliferation by enhancing the sensitivity to apoptosis in a cell cycle-dependent manner.

Academic Significance and Societal Importance of the Research Achievements

本研究により明らかとなった、食品成分BITCのMis12減少を介したがん細胞増殖抑制作用は、食品成分のもつ健康機能や安全性の科学的理解に大きく貢献するだけでなく、新規薬剤の開発に貢献することが期待される。さらに本研究により確立された出芽酵母スクリーニングシステムは、BITCの細胞増殖抑制作用に関連した標的遺伝子を安価・容易・選択性高く同定できたことから、ヒトにおける食品機能の統合的理解を目指す研究へと展開するための分子基盤を与える現実性の高い評価モデルとして、BITC以外の食品成分が標的とする分子の探索研究に汎用されることが今後期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (39 results)

All 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (15 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 15 results,  Open Access: 3 results) Presentation (19 results) (of which Int'l Joint Research: 7 results,  Invited: 5 results) Book (2 results) Remarks (1 results)

  • [Int'l Joint Research] Dalian Polytechnic University(中国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Dalian Polytechnic University(中国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Yeast screening system reveals the inhibitory mechanism of cancer cell proliferation by benzyl isothiocyanate through down-regulation of Mis122019

    • Author(s)
      Abe-Kanoh Naomi、Kunisue Narumi、Myojin Takumi、Chino Ayako、Munemasa Shintaro、Murata Yoshiyuki、Satoh Ayano、Moriya Hisao、Nakamura Yoshimasa
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 8866-8866

    • DOI

      10.1038/s41598-019-45248-2

    • NAID

      120006648600

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of benzyl isothiocyanate extracted from mashed green papaya by distillation2019

    • Author(s)
      Nakamura Toshiyuki、Murata Yoshiyuki、Nakamura Yoshimasa
    • Journal Title

      Food Chemistry

      Volume: 299 Pages: 125118-125118

    • DOI

      10.1016/j.foodchem.2019.125118

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Covalent Modification of Phosphatidylethanolamine by Benzyl Isothiocyanate and the Resultant Generation of Ethanolamine Adduct as Its Metabolite2019

    • Author(s)
      Nakamura Toshiyuki、Hirakawa Miho、Nakamura Yoshimasa、Ishisaka Akari、Kitamoto Noritoshi、Murakami Akira、Kato Yoji
    • Journal Title

      Chemical Research in Toxicology

      Volume: 32 Issue: 4 Pages: 638-644

    • DOI

      10.1021/acs.chemrestox.8b00331

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Benzyl isothiocyanate attenuates the hydrogen peroxide-induced interleukin-13 expression through glutathione S-transferase P induction in T lymphocytic leukemia cells2018

    • Author(s)
      Tang Yue、Naito Sho、Abe-Kanoh Naomi、Ogawa Seiji、Yamaguchi Shu、Zhu Beiwei、Murata Yoshiyuki、Nakamura Yoshimasa
    • Journal Title

      Journal of Biochemical and Molecular Toxicology

      Volume: なし Issue: 6

    • DOI

      10.1002/jbt.22054

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lycii fructus extract ameliorates hydrogen peroxide-induced cytotoxicity through indirect antioxidant action2018

    • Author(s)
      Xu Wensi、Saiki Shunya、Myojin Takumi、Liu Yujia、Zhu Beiwei、Murata Yoshiyuki、Ashida Hitoshi、Tsunenaga Makoto、Nakamura Yoshimasa
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 82 Issue: 10 Pages: 1812-1820

    • DOI

      10.1080/09168451.2018.1487274

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Phenethyl isothiocyanate activates leptin signaling and decreases food intake2018

    • Author(s)
      Yagi Miho、Nakatsuji Yukiko、Maeda Ayumi、Ota Hiroki、Kamikubo Ryosuke、Miyoshi Noriyuki、Nakamura Yoshimasa、Akagawa Mitsugu
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 11 Pages: e0206748-e0206748

    • DOI

      10.1371/journal.pone.0206748

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Benzyl isothiocyanate ameliorates lipid accumulation in 3T3-L1 preadipocytes during adipocyte differentiation2018

    • Author(s)
      Liang Ying、Sasaki Ikumi、Takeda Yuki、Zhu Beiwei、Munemasa Shintaro、Nakamura Toshiyuki、Murata Yoshiyuki、Nakamura Yoshimasa
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 82 Issue: 12 Pages: 2130-2139

    • DOI

      10.1080/09168451.2018.1514247

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Methyl-β-cyclodextrin potentiates the BITC-induced anti-cancer effect through modulation of the Akt phosphorylation in human colorectal cancer cells2018

    • Author(s)
      Yang Qifu、Miyagawa Miku、Liu Xiaoyang、Zhu Beiwei、Munemasa Shintaro、Nakamura Toshiyuki、Murata Yoshiyuki、Nakamura Yoshimasa
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 82 Issue: 12 Pages: 2158-2167

    • DOI

      10.1080/09168451.2018.1514249

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Flavonoid metabolism: the interaction of metabolites and gut microbiota.2018

    • Author(s)
      Murota K, Nakamura Y, Uehara M.
    • Journal Title

      Biosci Biotechnol Biochem.

      Volume: 82 Issue: 4 Pages: 600-610

    • DOI

      10.1080/09168451.2018.1444467

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Physiological relevance of covalent protein modification by dietary isothiocyanates2018

    • Author(s)
      Nakamura Toshiyuki、Abe-Kanoh Naomi、Nakamura Yoshimasa
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 62 Issue: 1 Pages: 11-19

    • DOI

      10.3164/jcbn.17-91

    • NAID

      130006301253

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] (-)-Epigallocatechin-3-gallate inhibits human angiotensin-converting enzyme activity through an autoxidation-dependent mechanism2017

    • Author(s)
      Liu Zhe、Nakashima Sayaka、Nakamura Toshiyuki、Munemasa Shintaro、Murata Yoshiyuki、Nakamura Yoshimasa
    • Journal Title

      J Biochem Mol Toxicol

      Volume: 31 Issue: 9 Pages: e21932-e21932

    • DOI

      10.1002/jbt.21932

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Inhibition of phosphatidylinositide 3-kinase ameliorates antiproliferation by benzyl isothiocyanate in human colon cancer cells2017

    • Author(s)
      Liu Xiaoyang、Takano Chiaki、Shimizu Tomomi、Yokobe Shintaro、Abe-Kanoh Naomi、Zhu Beiwei、Nakamura Toshiyuki、Munemasa Shintaro、Murata Yoshiyuki、Nakamura Yoshimasa
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 491 Issue: 1 Pages: 209-216

    • DOI

      10.1016/j.bbrc.2017.07.078

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Benzyl isothiocyanate ameliorates acetaldehyde-induced cytotoxicity by enhancing aldehyde dehydrogenase activity in murine hepatoma Hepa1c1c7 cells2017

    • Author(s)
      Liu Yujia、Yamanaka Momoko、Abe-Kanoh Naomi、Liu Xiaoyang、Zhu Beiwei、Munemasa Shintaro、Nakamura Toshiyuki、Murata Yoshiyuki、Nakamura Yoshimasa
    • Journal Title

      Food and Chemical Toxicology

      Volume: 108 Pages: 305-313

    • DOI

      10.1016/j.fct.2017.08.016

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 3,4-Dihydroxyphenylacetic acid is a potential aldehyde dehydrogenase inducer in murine hepatoma Hepa1c1c7 cells2017

    • Author(s)
      Liu Yujia、Kurita Ayuki、Nakashima Sayaka、Zhu Beiwei、Munemasa Shintaro、Nakamura Toshiyuki、Murata Yoshiyuki、Nakamura Yoshimasa
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 81 Issue: 10 Pages: 1978-1983

    • DOI

      10.1080/09168451.2017.1361809

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Inhibition of phosphatidylinositide 3-kinase impairs the benzyl isothiocyanate-induced accumulation of autophagic molecules and Nrf2 in human colon cancer cells2017

    • Author(s)
      Liu Xiaoyang、Abe-Kanoh Naomi、Liu Yujia、Zhu Beiwei、Munemasa Shintaro、Nakamura Toshiyuki、Murata Yoshiyuki、Nakamura Yoshimasa
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 81 Issue: 11 Pages: 2212-2215

    • DOI

      10.1080/09168451.2017.1374830

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 食品成分の化学構造から見る機能性発現の分子機構2019

    • Author(s)
      中村宜督
    • Organizer
      第73回 日本栄養・食糧学会大会・シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 食品由来ポリフェノール類がアセトアルデヒドの皮膚表皮細胞への毒性に与える影響2019

    • Author(s)
      明神 匠、Xu Wensi、中村俊之、宗正晋太郎、村田芳行、中村宜督
    • Organizer
      日本農芸化学会中四国支部第54回講演会(岡山)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Inhibition of drug resistance mechanisms ameliorates the benzyl isothiocyanate- induced antiproliferation in human colorectal cancer cells2019

    • Author(s)
      Yoshimasa Nakamura
    • Organizer
      The 7th International Conference on Food Factors (ICoFF2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Difference in antioxidant capacity of rice extracts among rice categories and degree of milling and processing2019

    • Author(s)
      Hongyan Wu, Miho Hirooka, Toshiyuki Nakamura, Shintaro Munemasa, Yoshiyuki Murata, Yoshimasa Nakamura
    • Organizer
      The 7th International Conference on Food Factors (ICoFF2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Benzyl isothiocyanate enhances insulin signaling in adipocytes2019

    • Author(s)
      Sayuri Nakata, Ying Liang, Toshiyuki Nakamura, Shintaro Munemasa, Yoshiyuki Murata, Yoshimasa Nakamura
    • Organizer
      The 7th International Conference on Food Factors (ICoFF2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Modulating effects of polyphenols on the acetaldehyde-induced cytotoxicity in human keratinocyte HaCaT cells2019

    • Author(s)
      Takumi Myojin, Wensi Xu, Shintaro Munemasa, Toshiyuki Nakamura, Yoshiyuki Murata, Yoshimasa Nakamura
    • Organizer
      The 9th International Conference on Polyphenols and Health (ICPH 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of the target proteins of quercetin glycoside catabolites as cytoprotective agent2019

    • Author(s)
      Kouki Morita, Sayaka Nakashima, Toshiyuki Nakamura, Shintaro Munemasa, Yoshiyuki Murata, Yoshimasa Nakamura
    • Organizer
      The 9th International Conference on Polyphenols and Health (ICPH 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Involvement of the phosphatidylinositide 3-kinase pathway in the resistant mechanisms against benzyl isothiocyanate in human colorectal cancer cells2018

    • Author(s)
      Yoshimasa Nakamura
    • Organizer
      Division of Agricultural and Food Chemistry, Functional Foods Session, 256th ACS National Meeting (Boston)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Chlorogenic acid ameliorates acetaldehyde-induced cytotoxicity in murine hepatoma Hepa1c1c7 cells2018

    • Author(s)
      Xu Wensi、Liu Yujia、宗正晋太郎、中村俊之、村田芳行、中村宜督
    • Organizer
      日本農芸化学会中四国支部第51回講演会(山口)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 青パパイヤ蒸留抽出液の生理活性および安定性の評価2018

    • Author(s)
      中村俊之、村田芳行、中村宜督
    • Organizer
      第23回日本フードファクター学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 食用花に含まれる色素aureusidinの合成と生体内抗酸化作用2018

    • Author(s)
      中島清花,清田洋正,中村俊之,宗正晋太郎,村田芳行,中村宜督
    • Organizer
      日本農芸化学会中四国支部第53回講演会(高知)
    • Related Report
      2018 Annual Research Report
  • [Presentation] ベンジルイソチオシアネートの脂肪蓄積抑制作用とその分子機構2018

    • Author(s)
      佐々木郁実,Liang Ying,竹田有希,中村俊之,宗正晋太郎,村田芳行,中村宜督
    • Organizer
      日本農芸化学会中四国支部第50回記念講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Benzyl isothiocyanate enhances glucose uptake and lipid accumulation via PI3K/Akt signaling pathway in 3T3-L1 adipocytes2018

    • Author(s)
      Ying Liang,佐々木郁実,竹田有希,中村俊之,宗正信太郎,村田芳行, 中村宜督
    • Organizer
      日本農芸化学会中四国支部第50回記念講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Methyl-β-cyclodextrin potentaited the BITC-induced anti-cancer effect through modulation of the PI3K/PDK1/Akt pathway in human colorectal cancer cells2018

    • Author(s)
      Qifu Yang, 中村 俊之, 宗正 晋太郎, 村田 芳行, 中村 宜督
    • Organizer
      日本農芸化学会中四国支部第50回記念講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Phenolic acid catabolites are predominant biologically active compounds derived from quercetin glycosides2017

    • Author(s)
      Yoshimasa Nakamura
    • Organizer
      8th International Conference on Polyphenols and Health (ICPH2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] フラボノイド配糖体代謝物の生体防御賦活作用2017

    • Author(s)
      中村宜督
    • Organizer
      日本農芸化学会中四国支部第48回講演会シンポジウム「生物資源を活用した応用研究」
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ベンジルイソチオシアネートの脂肪蓄積抑制作用とその分子機構2017

    • Author(s)
      佐々木郁実、Liang Ying、竹田有希、中村俊之、宗正晋太郎、村田芳行、中村宜督
    • Organizer
      フードサイエンスフォーラム第23 回学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Molecular mechanisms underlying aldehyde dehydrogenase induction by phenolic acid catabolites of quercetin glycosides2017

    • Author(s)
      Yujia Liu, Ayuki Kurita, Sayaka Nakashima, Shintaro Munemasa, Toshiyuki Nakamura, Yoshiyuki Murata, Yoshimasa Nakamura
    • Organizer
      日本農芸化学会 2017年度関西・中四国・西日本支部合同大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] A link between benzyl isothiocyanate-induced autophagy and Nrf2/Keap1 regulation in human colon cancer cells2017

    • Author(s)
      Xiaoyang Liu, Naomi Abe-Kanoh, Yujia Liu, Shintaro Munemasa, Toshiyuki Nakamura, Yoshiyuki Murata, Yoshimasa Nakamura
    • Organizer
      日本農芸化学会 2017年度関西・中四国・西日本支部合同大会
    • Related Report
      2017 Annual Research Report
  • [Book] エッセンシャル食品化学2018

    • Author(s)
      中村 宜督、榊原 啓之、室田 佳恵子
    • Total Pages
      256
    • Publisher
      講談社
    • ISBN
      9784065133415
    • Related Report
      2018 Annual Research Report
  • [Book] Visual栄養学テキスト食べ物と健康 I 食品学総論 食品の成分と機能 2章 食品の機能 1-3 脂質2017

    • Author(s)
      中村宜督
    • Total Pages
      11
    • Publisher
      中山書店
    • ISBN
      9784521742878
    • Related Report
      2017 Annual Research Report
  • [Remarks] https://yossan24okayama.jimdofree.com/

    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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