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Elucidation of mechanism of prooxidant effect on cancer cells by polyphenols

Research Project

Project/Area Number 20H03926
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 58020:Hygiene and public health-related: including laboratory approach
Research InstitutionHokkaido University

Principal Investigator

Hosokawa Toshiyuki  北海道大学, 高等教育推進機構, 名誉教授 (00157025)

Co-Investigator(Kenkyū-buntansha) 斎藤 健  北海道大学, 保健科学研究院, 客員研究員 (40153811)
佐藤 伸  青森県立保健大学, 健康科学部, 教授 (40310099)
向井 友花  神奈川県立保健福祉大学, 保健福祉学部, 教授 (60331211)
藏崎 正明  北海道大学, 地球環境科学研究院, 客員研究員 (80161727)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Fiscal Year 2022: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2021: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2020: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Keywordsポリフェノール / 抗酸化作用 / プロオキシダント作用 / 癌細胞 / アポトーシス / プロオキシダント / ガン細胞
Outline of Research at the Start

ポリフェノール類は抗酸化作用を有するが、最近真逆の酸化促進作用も示すことが報告されている。つまり、ポリフェノール類が未分化細胞であるガン細胞等で遺伝子に定められた細胞死・アポトーシスを誘導することが報告されている。通常、抗アポトーシス作用を示すポリフェノールが、何故ガン細胞でアポトーシスを誘導するのかは未だ不明のままである。本研究では、ポリフェノール類による抗ガン作用がどのような機構によって起こるのかを正常細胞とガン細胞の双方に対するポリフェノール類の作用を明らかにすることで解明しようとしている。本研究の達成により、植物成分であるポリフェノール類により負担の少ない抗ガン剤の開発が期待される。

Outline of Final Research Achievements

HepG2 and Caco-2 cells derived from human cancer cells were exposed to various concentrations of resveratrol or epigallocatechin gallate. As results, cell viavility of the human cancer cells exposed to the polyphenol was increased in a dose-dependent manner, and the oxidative state in the cells was enhanced.
Analyses by Western blotting and other biochemical and cell biological methods confirmed that exposure to polyphenols in the human cancer cells induced apoptosis via autophagy. On the other hand, when human normal hepatocytes, HUCPG cells, were exposed to resveratrol, no significant changes in apoptotic factors were observed, and there was no sign of apoptosis induction in the cells.
From these results, it was clarified that apoptosis was induced only in cancer cells when exposed to polyphenols.

Academic Significance and Societal Importance of the Research Achievements

世界的に年々増加している様々な癌の治療において化学療法は重要な選択肢の一つであるが、しばしばその重篤な副作用が大きな問題となっている。安全で副作用の少ない抗癌剤あるいは抗癌補助剤の開発は癌治療戦略において緊喫の学術意義のある課題である。本研究で示された植物成分の一種であり毒性が少ないポリフェノール類が癌細胞にアポトーシスを誘導するという実験結果は将来の安全な抗癌補助剤の開発のための重要なステップになることが大いに期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (20 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 9 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 3 results) Book (1 results)

  • [Int'l Joint Research] Jahangirnagar University(バングラデシュ)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Green synthesized silver nanoparticles-mediated cytotoxic effect in colorectal cancer cells: NF-κB signal induced apoptosis through autophagy2021

    • Author(s)
      Mahmuda Akter, A.K.M. Atique Ullah, Subrata Banik, Md. Tajuddin Sikder, Toshiyuki Hosokawa, Takeshi Saito, Masaaki Kurasaki
    • Journal Title

      Biological Trace Element Research

      Volume: 199(9) Issue: 9 Pages: 3272-3286

    • DOI

      10.1007/s12011-020-02463-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Environmental arsenic exposure and its contribution to human diseases, toxicity mechanism and management2021

    • Author(s)
      Rahaman Md. Shiblur、Rahman Md. Mostafizur、Mise Nathan、Sikder Md. Tajuddin、Ichihara Gaku、Uddin Md. Khabir、Kurasaki Masaaki、Ichihara Sahoko
    • Journal Title

      Environmental Pollution

      Volume: 289 Pages: 117940-117940

    • DOI

      10.1016/j.envpol.2021.117940

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pb (II) remediation from aqueous environment using chitosan-activated carbon-Polyvinyl alcohol composite beads2021

    • Author(s)
      Mahmuda Akter, Noriko Hirase, Md. Tajuddin Sikder, Md. Mostafizur Rahman, Toshiyuki Hosokawa, Takeshi Saito, Masaaki Kurasaki
    • Journal Title

      Water Air and Soil Pollution

      Volume: 232 Issue: 7

    • DOI

      10.1007/s11270-021-05243-8

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Amelioration of Metal-Induced Cellular Stress by alpha-Lipoic Acid and Dihydrolipoic Acid through Antioxidative Effects in PC12 Cells and Caco-2 Cells2021

    • Author(s)
      Kaniz Fatima Binte Hossain, Mahmuda Akter, Md Mostafizur Rahman, Md Tajuddin Sikder, Shiblur Rahaman, Shojiro Yamasaki, Goh Kimura, Tomomi Tomihara, Masaaki Kurasaki, Takeshi Saito
    • Journal Title

      International Journal of Environmental Research and Public Health

      Volume: 18 Issue: 4 Pages: 2126-2126

    • DOI

      10.3390/ijerph18042126

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] <p>Modulation of Chronic Inflammation by Quercetin: The Beneficial Effects on Obesity</p>2020

    • Author(s)
      Sato Shin、Mukai Yuuka
    • Journal Title

      Journal of Inflammation Research

      Volume: Volume 13 Pages: 421-431

    • DOI

      10.2147/jir.s228361

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amelioration of butylated hydroxytoluene against inorganic mercury induced cytotoxicity and mitochondrial apoptosis in PC12 cells via antioxidant effects2020

    • Author(s)
      Kaniz Fatima Binte Hossain, Toshiyuki Hosokawa, Takeshi Saito, Masaaki Kurasaki
    • Journal Title

      Food and Chemical Toxicology

      Volume: 146 Pages: 111819-111819

    • DOI

      10.1016/j.fct.2020.111819

    • NAID

      120007173914

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of curcumin, D-pinitol alone or in combination in cytotoxicity induced by arsenic in PC12 cells2020

    • Author(s)
      Md Shiblur Rahaman, Shojiro Yamasaki, Kaniz Fatima Binte Hossain, Toshiyuki Hosokawa, Takeshi Saito, Masaaki Kurasaki,
    • Journal Title

      Food and Chemical Toxicology

      Volume: 144 Pages: 111577-111577

    • DOI

      10.1016/j.fct.2020.111577

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Curcumin alleviates arsenic-induced toxicity in PC12 cells via modulating autophagy/apoptosis2020

    • Author(s)
      Md Shiblur Rahaman, Subrata Banik, Mahmuda Akter, Md Mostafizur Rahman, Md Tajuddin Sikder, Toshiyuki Hosokawa, Takeshi Saito, Masaaki Kurasaki
    • Journal Title

      Ecotoxicology and Environmental Safety

      Volume: 200 Pages: 110756-110756

    • DOI

      10.1016/j.ecoenv.2020.110756

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Analysis of Cadmium, Epigallocatechin Gallate, and Vitamin C Co-exposure on PC12 Cellular Mechanisms2020

    • Author(s)
      Serene Ezra Corpus Bondad, Masaaki Kurasaki
    • Journal Title

      Biological Trace Element Research

      Volume: 198 Issue: 2 Pages: 627-635

    • DOI

      10.1007/s12011-020-02097-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] ポリフェノール類によるHepG2細胞におけるアポトーシス誘導機構2023

    • Author(s)
      蔵崎正明,アクター マームーダ,佐藤伸,向井友花,齋藤健,細川敏幸
    • Organizer
      第93回日本衛生学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Epigallocatechin-3- gallate induced anticancer efficiency on Caco2 cells through the inhibition of cell proliferation following apoptosis2023

    • Author(s)
      M. Kurasaki, M. Akter, T. Saito, T. Hosokawa
    • Organizer
      Scottish Section Conference 2023 Diet and Health Inequalities
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Imbalance between ROS expression and their metabolic mechanisms causes accelerated aging in senescence accelerated mouse P102022

    • Author(s)
      T. Saito, T. Kawahara, T. Hosokawa, M. Kurasaki
    • Organizer
      8th International Symposium Federation of European Societies on Trace Elements and Minerals
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Epigallocatechin-3-gallate and resveratrol showed anticancer ability on HepG2 and Caco2 cells through intrinsic apoptosis pathway following autophagy2022

    • Author(s)
      M. Kurasaki, M. Akter, S. Sato, Y. Mukai, T. Hosokawa, T. Saito
    • Organizer
      8th International Symposium Federation of European Societies on Trace Elements and Minerals
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 授乳期の母親の緑茶摂取は継続的な高脂肪摂取による仔ラットの肝臓資質蓄積を抑制する2021

    • Author(s)
      山﨑尚二郎、Ketema Rahel、大野由貴、小泉一成、戴 寧、佐藤 伸、蔵崎正明、細川敏幸、齋藤 健
    • Organizer
      第91回日本衛生学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] エピガロカテキン-3-ガレートの結腸直腸癌細胞における抗癌効果およびそのメカニズム2021

    • Author(s)
      Mahmuda Akter、細川敏幸、齋藤 健、蔵崎正明
    • Organizer
      第91回日本衛生学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 母ラットの高脂肪食、緑茶抽出物が仔ラットのオートファジー機能へ及ぼす影響2021

    • Author(s)
      大野由貴、山﨑尚二郎、Ketema Rahel、小泉一成、戴 寧、佐藤 伸、蔵崎正明、齋藤 健
    • Organizer
      第91回日本衛生学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] PC12細胞におけるエピガロカテキンガレート熱酸化生成物のカドミウム毒性に対する影響2021

    • Author(s)
      Bondad Serene Ezra Corpus、沖野龍文、齋藤 健、蔵崎正明
    • Organizer
      第91回日本衛生学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] PC12細胞における銀ナノ粒子の細胞毒性効果とそのメカニズム2020

    • Author(s)
      Mahmuda Akter、齋藤健太郎、江良宙夢。細川敏幸、齋藤 健、蔵崎正明
    • Organizer
      第31回日本微量元素学会
    • Related Report
      2020 Annual Research Report
  • [Book] Design of Materials and Technologies for Environmental Remediation, Hdb Env Chem2023

    • Author(s)
      Shunitz Tanaka, Masaaki Kurasaki, Masaaki Morikawa, and Yuichi Kamiya (eds.)
    • Total Pages
      1183
    • Publisher
      Springer Nature
    • ISBN
      9789811952357
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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