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Role of autophagy on cell growth and differenciation by phytoestorogens

Research Project

Project/Area Number 16K00902
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Eating habits
Research InstitutionNational Institutes of Biomedical Innovation, Health and Nutrition

Principal Investigator

ISHIMI YOSHIKO  国立研究開発法人医薬基盤・健康・栄養研究所, 国立健康・栄養研究所, シニアアドバイザー (50154159)

Co-Investigator(Kenkyū-buntansha) 石見 幸男  茨城大学, 理工学研究科(理学野), 教授 (80159772)
Co-Investigator(Renkei-kenkyūsha) TOUSEN Yuko  国立研究開発法人医薬基盤・健康・栄養研究所, 国立健康・栄養研究所・食品保健機能研究部食品安全, 機能研究室長 (20360092)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords植物性エストロゲン / 大豆イソフラボン / 自食作用 / 細胞周期 / 骨芽細胞 / 乳がん細胞 / 細胞増殖 / 細胞分化 / オートファジー / 脂肪細胞
Outline of Final Research Achievements

The relationship between autophagy and differentiation in adipocytes and osteoblasts was examined. The mRNA expression of autophagy-related genes of adipocyte MC3T3-L1 cells increased on day 2 of the culture.These gene expressions in osteoblast MC3T3-E1 cells increased depending on cell growth. Isoflavone decreased the gene expressions in adipocytes but enhanced them in osteoblasts.These results suggest that autophagy may be involved in cell growth and differentiation of both cells.
Effect of inhibitors for autophagy on cell growth cultured in the presence of equol was examined in breast cancer MCF-7 cells. The presence of bafilomycin decreased the proportion of S phase cells and the chromatin-bound MCM2-7 proteins, while the amounts of HIF-1A proteins increased. Interaction between MCM2-7 and HIF-1A was detected by immuno-precipitation. Thus, the cell cycle progression in G1 phase proceeds by autophagic degradation of HIF-1A which may act as a negative regulator of MCM2-7 function.

Academic Significance and Societal Importance of the Research Achievements

本研究において、骨・脂質代謝に対する植物性エストロゲンの作用とそのメカニズムを明らかにすることで、植物性エストロゲンの有効性・安全性評価に貢献する。また、イソフラボン代謝産物エクオールをはじめとする植物性エストロゲンは、エストロゲン様作用を示すことから、生殖関連組織の細胞増殖に対する影響を評価する必要がある。本研究では、標的細胞のDNA合成の促進を細胞周期の進行制御、さらにはオートファジーの役割に注目して検討した。植物エストロゲンの細胞増殖と分化に対する作用に関して新たな科学的根拠が蓄積されたことから、本研究は、植物性エストロゲンを含む食品の安全確保に貢献するものと考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (18 results)

All 2019 2018 2017 2016

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (3 results)

  • [Journal Article] Comparison of Nutrient Reference Values for Food Labeling in Japan with CODEX Recommendations, Based on DRIs and Nutrient Intake in Japan2019

    • Author(s)
      Tsuboyama-Kasaoka N, Takimoto H, Ishimi Y.
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 65 Issue: 1 Pages: 102-105

    • DOI

      10.3177/jnsv.65.102

    • NAID

      130007604899

    • ISSN
      0301-4800, 1881-7742
    • Year and Date
      2019-02-28
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Resistant starch attenuates bone Loss in ovariectomised mice by regulating the intestinal microbiota and bone-marrow inflammation.2019

    • Author(s)
      Tousen Y, Matsumoto Y, Nagahata Y, Kobayashi I, Inoue M, Ishimi Y.
    • Journal Title

      Nutrients.

      Volume: 11(2) Issue: 2 Pages: 297-297

    • DOI

      10.3390/nu11020297

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of daidzein and equol on DNA replication in MCF-7 cells2018

    • Author(s)
      Tsuji Mako、Tanaka Tomoki、Nagashima Ryosuke、Sagisaka Yuka、Tousen Yuko、Nishide Yoriko、Ishimi Yoshiko、Ishimi Yukio
    • Journal Title

      Journal of Biochemistry

      Volume: 163 Issue: 5 Pages: 371-380

    • DOI

      10.1093/jb/mvy006

    • NAID

      40021555315

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] β-Carotene prevents bone loss in hind limb unloading mice2018

    • Author(s)
      Matsumoto Yu, Tousen Y and Ishimi Y.
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 63 Issue: 1 Pages: 42-49

    • DOI

      10.3164/jcbn.17-86

    • NAID

      130007387114

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isoflavones and green kiwifruit: A pilot study assessing the effects on equol production, bone turnover and gut microflora in healthy postmenopausal New Zealand women.2018

    • Author(s)
      Kruger MC, Middlemiss C, Katsumata S, Tousen Y, Ishimi Y
    • Journal Title

      Asia Pac J Clin Nutr

      Volume: 27 Pages: 347-358

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The combined effects of soya isoflavones and resistant starch on equol production and trabecular bone loss in ovariectomised mice.2016

    • Author(s)
      Tousen Y, Matsumoto Y, Matsumoto C, Nishide Y, Nagahata Y, Kobayashi I, Ishimi Y
    • Journal Title

      Br J Nutr.

      Volume: 116(2) Issue: 2 Pages: 247-57

    • DOI

      10.1017/s0007114516001537

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combined effects of soy isoflavones and milk basic protein on bone mineral density in hind-limb unloaded mice2016

    • Author(s)
      Matsumoto Y, Tousen Y, Nishide Y, Tadashi M, Kato K, Ishimi Y
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 58 Issue: 2 Pages: 141-145

    • DOI

      10.3164/jcbn.14-137

    • NAID

      130005132518

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Combined Effects of Soy Isoflavones and Docosahexaenoic Acid on Osteoclast Formation.2016

    • Author(s)
      Katsumata S、Plimmer G、Tadaishi M、Tousen Y、Ishimi Y、Kruger MC
    • Journal Title

      Journal of Food and Nutrition Research

      Volume: 4 Pages: 429-435

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 閉経後モデルマウスにおける葛の花由来イソフラボン抽出物の安全性・有効性評価-大豆イソフラボンとの比較-2018

    • Author(s)
      東泉裕子、西出依子、竹林純、梅垣敬三、渕野裕之、河野徳昭、乾貴幸、吉松嘉代、川原信夫、石見佳子
    • Organizer
      第72回日本栄養・食糧学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] HIF-1αとMCM2-7との相互作用-オートファジーとの関係2018

    • Author(s)
      宮本優眞、山崎美穂、石見幸男
    • Organizer
      2018年度日本生化学会関東支部例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Assessment of safety and efficacy of phytoestrogen, isoflavone, on bone metabolism in animal models.2018

    • Author(s)
      Ishimi Y、Tousen Y
    • Organizer
      8th Annual World Congress of Molecular & Cell Biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] カンゾウ由来健康食品の安全性・有効性評価2018

    • Author(s)
      石見佳子、竹林純、東泉裕子、山内淳、渕野裕之、河野徳昭、乾貴幸、吉松嘉代、川原信夫
    • Organizer
      第72回日本栄養・食糧学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 非荷重モデルマウスの骨密度低下に対するβ-カロテン摂取の影響2018

    • Author(s)
      東泉裕子、松本雄宇、石見佳子
    • Organizer
      第65回日本栄養改善学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The effects of resistant starch on bone loss via intestinal microbiota and inflammation in ovariectomised mice.2017

    • Author(s)
      Tousen Y、Matsumoto Y、Nagahata Y、Ishimi Y
    • Organizer
      IUNS 21st International Congress of Nutrition 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大豆イソフラボンによる乳がん由来MCF-7細胞DNA複製の促進2016

    • Author(s)
      石見幸男、匂坂有花、田中智紀、石見佳子
    • Organizer
      平成28年度日本生化学会関東支部例会、
    • Place of Presentation
      自治医科大学
    • Related Report
      2016 Research-status Report
  • [Book] すべての診療科で役立つ栄養学と食事・栄養療法2019

    • Author(s)
      石見佳子
    • Total Pages
      247
    • Publisher
      羊土社
    • ISBN
      9784758108980
    • Related Report
      2018 Annual Research Report
  • [Book] 食品機能性成分の吸収・代謝・作用機序2018

    • Author(s)
      石見佳子
    • Total Pages
      316
    • Publisher
      シーエムシー出版
    • ISBN
      9784781313276
    • Related Report
      2018 Annual Research Report
  • [Book] 食と微生物の事典2017

    • Author(s)
      石見佳子他
    • Total Pages
      490
    • Publisher
      朝倉書店
    • ISBN
      9784254431216
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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