Synergistic anti-cancer effects of rice bran components and their mechanisms of action

• Project/Area Number: 17K07803
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Tohoku University
• Principal Investigator: Eitsuka Takahiro 東北大学, 農学研究科, 准教授 (30445895)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 米ぬか / トコトリエノール / フェルラ酸 / 癌抑制 / テロメラーゼ / 相乗効果 / 相乗作用 / 癌 / 食品 / 脂質

Outline of Final Research Achievements

Rice bran consists of many functional compounds, including phytosterols, vitamin E (tocopherol and tocotrienol), ferulic acid, and gamma-oryzanol. We clarified the synergistic anti-cancer action (cell growth suppression and telomerase inhibition) of tocotrienol and ferulic acid. This synergistic effect is attributed to an increase in the cellular concentration of tocotrienol through inhibition of its metabolism by ferulic acid. Ferulic acid analogs containing a phenylpropanoid backbone can also synergize with tocotrienol. Our findings suggest the application of rice bran components to cancer prevention and therapy.

Academic Significance and Societal Importance of the Research Achievements

本研究は、米ぬか成分の潜在的可能性を究明し、“米成分による癌予防”の道を拓くものである。米ぬかに含まれる成分同士の相乗効果とその機構を解明しようとする研究は国内外で皆無であり、本研究の新規性は極めて高い。トコトリエノールの癌抑制に相乗効果をもたらす食品機能分子をフェルラ酸の類縁体から見出したことで、トコトリエノールとの食べ合わせに理想的な食品を提案することができるため、栄養指導の観点から癌を予防することが可能になる。また、米ぬかを高付加価値化できるため、米の消費拡大と食品産業の活性化が図られるとともに、高齢化が進む日本人の健康維持への貢献、さらには増大する国民医療費の抑制にもつながる。

Research Products

• [Journal Article] Analysis of oxidation products of α-tocopherol in extra virgin olive oil using liquid chromatography?tandem mass spectrometry (2020)
  • Author(s): Tanno Rena、Kato Shunji、Shimizu Naoki、Ito Junya、Sato Shuntaro、Ogura Yusuke、Sakaino Masayoshi、Sano Takashi、Eitsuka Takahiro、Kuwahara Shigefumi、Miyazawa Teruo、Nakagawa Kiyotaka
  • Journal Title: Food Chemistry Volume: 306 Pages: 125582-125582
  • DOI: 10.1016/j.foodchem.2019.125582
  • Peer Reviewed
• [Journal Article] Efficient immortalization of human dental pulp stem cells with expression of cell cycle regulators with the intact chromosomal condition (2020)
  • Author(s): Orimoto Ai、Kyakumoto Seiko、Eitsuka Takahiro、Nakagawa Kiyotaka、Kiyono Tohru、Fukuda Tomokazu
  • Journal Title: PLOS ONE Volume: 15 Issue: 3 Pages: e0229996-e0229996
  • DOI: 10.1371/journal.pone.0229996
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of mutant Cyclin-dependent-kinase, CyclinD, and TERT extends the proliferation period until senescence in chicken and Okinawa rail derived fibroblasts (2019)
  • Author(s): Katayama M, Kiyono T, Ohmaki H, Eitsuka T, Endo D, Inoue-Murayama M, Nakajima N, Onuma M, Fukuda T
  • Journal Title: Journal of Cellular Physiology Volume: 234 Issue: 5 Pages: 6709-6720
  • DOI: 10.1002/jcp.27417
  • Peer Reviewed
• [Journal Article] Establishment of immortalized primary cell from the critically endangered Bonin flying fox (Pteropus pselaphon) (2019)
  • Author(s): Tani T, Eitsuka T, Katayama M, Nagamine T, Nakaya Y, Suzuki H, Kiyono T, Nakagawa K, Inoue-Murayama M, Onuma M, Fukuda T
  • Journal Title: PLoS One Volume: 14 Issue: 8 Pages: e0221364-e0221364
  • DOI: 10.1371/journal.pone.0221364
  • NAID: 120006863529
  • Peer Reviewed / Open Access
• [Journal Article] Expression of human mutant cyclin dependent kinase 4, Cyclin D and telomerase extends the life span but does not immortalize fibroblasts derived from loggerhead sea turtle (Caretta caretta). (2018)
  • Author(s): Fukuda T, Eitsuka T, Donai K, Kurita M, Saito T, Okamoto H, Kinoshita K, Katayama M, Nitto H, Uchida T, Onuma M, Sone H, Inoue-Murayama M, Kiyono T.
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 9229-9229
  • DOI: 10.1038/s41598-018-27271-x
  • NAID: 120006979734
  • Peer Reviewed / Open Access
• [Journal Article] Efficient immortalization of cells derived from critically endangered Tsushima leopard cat (Prionailurus bengalensis euptilurus) with expression of mutant CDK4, Cyclin D1, and telomerase reverse transcriptase. (2018)
  • Author(s): Gouko R, Onuma M, Eitsuka T, Katayama M, Takahashi K, Nakagawa K, Inoue-Murayama M, Kiyono T, Fukuda T.
  • Journal Title: Cytotechnology Volume: 70 Issue: 6 Pages: 1619-1630
  • DOI: 10.1007/s10616-018-0254-0
  • Peer Reviewed
• [Journal Article] Modulation of Telomerase Activity in Cancer Cells by Dietary Compounds: A Review (2018)
  • Author(s): Eitsuka, T., Nakagawa, K., Kato, S., Ito, J., Otoki, Y., Takasu, S., Shimizu, N., Takahashi, T., Miyazawa, T.
  • Journal Title: Int. J. Mol. Sci. Volume: 19 Issue: 2 Pages: 478-478
  • DOI: 10.3390/ijms19020478
  • Peer Reviewed / Open Access
• [Journal Article] 脂溶性栄養成分によるがん抑制に関する食品学的研究 (2017)
  • Author(s): 永塚貴弘
  • Journal Title: 日本栄養食糧学会誌 Volume: 70 Pages: 263-269
  • Peer Reviewed
• [Journal Article] こめ油成分を活用した相乗的ながん抑制効果 (2017)
  • Author(s): 永塚 貴弘, 西田 浩志, 仲川 清隆, 宮澤 陽夫
  • Journal Title: オレオサイエンス Volume: 17 Pages: 261-268
  • NAID: 130007687673
• [Presentation] サメ肝油中スクアレンの酸化評価とα-トコフェロールによる酸化抑制 (2019)
  • Author(s): 清水直紀, 伊藤隼哉, 加藤俊治, 永塚貴弘, 齋藤哲男, 西田浩志, 仲川清隆
  • Organizer: 日本ビタミン学会
• [Presentation] こめ油成分による相乗的な癌細胞増殖阻害 (2018)
  • Author(s): 永塚 貴弘, 仲川 清隆, 宮澤 陽夫
  • Organizer: 日本油化学会第57回年会
• [Presentation] トコトリエノールとフェルラ酸による相乗的な癌抑制作用 (2018)
  • Author(s): 永塚貴弘、仲川清隆、宮澤陽夫
  • Organizer: 第29回ビタミンＥ研究会
• [Book] 食品機能性成分の吸収・代謝・作用機序 (2018)
  • Author(s): 永塚 貴弘
  • Publisher: シーエムシー出版