Searching for food components to promote removal of mutant cells

• Project/Area Number: 16K07726
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Hirosaki University
• Principal Investigator: Nagaosa Kaz 弘前大学, 地域戦略研究所, 准教授 (70401891)
• Co-Investigator(Kenkyū-buntansha): 中井 雄治 弘前大学, 地域戦略研究所, 教授 (10321788)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 癌予防 / 変異細胞除去 / 食品 / 細胞競合 / ショウジョウバエ

Outline of Final Research Achievements

There are many mutant cells which may turn to be tumor cells, in our body. Elimination of these cell would be important to prevent cancer. Using functional foods is good idea to facilitate the reaction, because intake of foods is an easy daily approach.
For finding such foods, we constructed the screening system using Drosophila, and found four foods which facilitated mutant cell-removal from 21 of candidates. Two of them also suppressed mutagen-derived Drosophila death, strongly suggested that they are cancer-preventing foods. Further investigation is required to determine whether this function is due to the removal of mutant cells. We also identified the functional components from one of the four. It will be possible to elucidate the mechanism for promoting mutant cell-elimination, using these molecules.

Academic Significance and Societal Importance of the Research Achievements

本研究により変異細胞の除去を促進する食品4品が見出された。うち2品（食品A、B）では変異原による動物個体の死が抑制され、A、Bの癌予防作用が強く示唆された。これらは新たな作用機序に基づく癌予防食品となることが期待される。哺乳類動物実験等を経て実用化が可能となれば社会的に大変意義深いものとなる。また、食品Cについては機能性成分の特定に成功した。これを利用した変異細胞除去促進機構の解析が可能となった点は学術的な意義は大きい。

Research Products

• [Journal Article] ショウジョウバエを用いた食品の機能性研究 (2019)
  • Author(s): 永長一茂, 中井雄治
  • Journal Title: Journal of Home Economics of Japan Volume: 70 Issue: 11 Pages: 770-777
  • DOI: 10.11428/jhej.70.770
  • NAID: 130007749744
  • ISSN: 0913-5227, 1882-0352
• [Journal Article] Inhibitory effects of viral infection on cancer development (2019)
  • Author(s): Rahmatika Dini、Kuroda Nanae、Min Zhang、Nainu Firzan、Nagaosa Kaz、Nakanishi Yoshinobu
  • Journal Title: Virology Volume: 528 Pages: 48-53
  • DOI: 10.1016/j.virol.2018.12.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dose-Dependent Increase of Nrf2 Target Gene Expression in Mice Exposed to Ionizing Radiation (2019)
  • Author(s): Miura Shuta、Yamaguchi Masaru、Yoshino Hironori、Nakai Yuji、Kashiwakura Ikuo
  • Journal Title: Radiation Research Volume: 191 Issue: 2 Pages: 176-188
  • DOI: 10.1667/rr15203.1
  • Peer Reviewed / Open Access
• [Journal Article] The Gα12/13-coupled receptor LPA4 limits proper adipose tissue expansion and remodeling in diet-induced obesity (2018)
  • Author(s): Yanagida Keisuke、Igarashi Hidemitsu、Yasuda Daisuke、Kobayashi Daiki、Ohto-Nakanishi Takayo、Akahoshi Noriyuki、Sekiba Atsushi、Toyoda Tsudoi、Ishijima Tomoko、Nakai Yuji、Shojima Nobuhiro、Kubota Naoto、Abe Keiko、Kadowaki Takashi、Ishii Satoshi、Shimizu Takao
  • Journal Title: JCI Insight Volume: 3 Issue: 24 Pages: 397293-397293
  • DOI: 10.1172/jci.insight.97293
  • Peer Reviewed / Open Access
• [Journal Article] The Anti-Arthritis Effect of Olive-Derived Maslinic Acid in Mice is Due to its Promotion of Tissue Formation and its Anti-Inflammatory Effects (2018)
  • Author(s): Shimazu Kyoko、Fukumitsu Satoshi、Ishijima Tomoko、Toyoda Tsudoi、Nakai Yuji、Abe Keiko、Aida Kazuhiko、Okada Shinji、Hino Akihiro
  • Journal Title: Molecular Nutrition & Food Research Volume: 63 Issue: 3
  • DOI: 10.1002/mnfr.201800543
  • Peer Reviewed / Open Access
• [Journal Article] Placenta Specific 8 Suppresses IL-18 Production through Regulation of Autophagy and Is Associated with Adult Still Disease (2018)
  • Author(s): Segawa Seiji、Kondo Yuya、Nakai Yuji、Iizuka Akira、Kaneko Shunta、Yokosawa Masahiro、Furuyama Kotona、Tsuboi Hiroto、Goto Daisuke、Matsumoto Isao、Sumida Takayuki
  • Journal Title: The Journal of Immunology Volume: 201 Issue: 12 Pages: 3534-3545
  • DOI: 10.4049/jimmunol.1800667
  • Peer Reviewed / Open Access
• [Journal Article] DNMTs and SETDB1 function as co-repressors in MAX-mediated repression of germ cell-related genes in mouse embryonic stem cells (2018)
  • Author(s): Tatsumi Daiki、Hayashi Yohei、Endo Mai、Kobayashi Hisato、Yoshioka Takumi、Kiso Kohei、Kanno Shinichiro、Nakai Yuji、Maeda Ikuma、Mochizuki Kentaro、Tachibana Makoto、Koseki Haruhiko、Okuda Akihiko、Yasui Akira、Kono Tomohiro、Matsui Yasuhisa
  • Journal Title: PLOS ONE Volume: 13 Issue: 11 Pages: e0205969-e0205969
  • DOI: 10.1371/journal.pone.0205969
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hepatic fatty acid biosynthesis in KK-Ay mice is modulated by administration of persimmon peel extract: A DNA microarray study (2018)
  • Author(s): Izuchi Ryoichi、Ishijima Tomoko、Okada Shinji、Abe Keiko、Nakai Yuji
  • Journal Title: Food Science & Nutrition Volume: 6 Issue: 6 Pages: 1657-1663
  • DOI: 10.1002/fsn3.728
  • NAID: 40021841979
  • Peer Reviewed / Open Access
• [Journal Article] Oral administration of edible wakame seaweed Undaria pinnatifida (wakame) modifies glucose and lipid metabolism in rats: a DNA microarray analysis. (2018)
  • Author(s): Yoshinaga, K., Nakai, Y., Izumi, H., Nagaosa, K., Ishijima, T., Nakano, T., Abe, K.
  • Journal Title: Mol. Nutr. Food Res. Volume: 印刷中 Issue: 12
  • DOI: 10.1002/mnfr.201700828
  • Peer Reviewed / Open Access
• [Journal Article] Combined loss of JMJD1A and JMJD1B reveals critical roles for H3K9 demethylation in the maintenance of embryonic stem cells and early embryogenesis. (2018)
  • Author(s): Kuroki, S., Nakai, Y., Maeda, R., Okashita, N., Akiyoshi, M., Yamaguchi, Y., Kitano, S., Miyachi, H., Nakato, R., Ichiyanagi, K., Shirahige, K., Kimura, H., Shinkai, Y., and Tachibana, M.
  • Journal Title: Stem Cell Rep. Volume: 10 Issue: 4 Pages: 1340-1354
  • DOI: 10.1016/j.stemcr.2018.02.002
  • NAID: 120006463740
  • Peer Reviewed / Open Access
• [Journal Article] Signaling pathway for phagocyte priming upon encounter with apoptotic cells (2017)
  • Author(s): Nonaka, S., Ando, Y., Kanetani, T., Hoshi, C., Nakai, Y., Nainu, F., Nagaosa, K., Shiratsuchi, A., and Nakanishi, Y
  • Journal Title: Journal of Biological Chemistry Volume: - Issue: 19 Pages: 8059-8072
  • DOI: 10.1074/jbc.m116.769745
  • NAID: 120006336006
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mechanisms and Significance of Phagocytic Elimination of Cells Undergoing Apoptotic Death (2017)
  • Author(s): Nonaka, S., Shiratsuchi, A., Nagaosa, K., and Nakanishi, Y.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 40 Issue: 11 Pages: 1819-1827
  • DOI: 10.1248/bpb.b17-00478
  • NAID: 130006191964
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive DNA microarray expression profiles of tumors in tenascin-C-knockout mice. (2017)
  • Author(s): Matsumoto, K., Nakai, Y., Hoshino, M., Yamazaki, K., Takioto, Y., Takadera, S., Nakagawa, T., Nishimura, R., and Kusakabe, M.
  • Journal Title: Biosci. Biotechnol. Biochem. Volume: 81 Issue: 10 Pages: 1926-1936
  • DOI: 10.1080/09168451.2017.1362975
  • Peer Reviewed
• [Journal Article] Overexpression of KCNJ2 in induced pluripotent stem cell-derived cardiomyocytes for the assessment of QT-prolonging drugs. (2017)
  • Author(s): Li, M., Kanda, Y., Ashihara, T., Sasano, T., Nakai, Y., Kodama, M., Hayashi, E., Sekino, Y., Furukawa, T., and Kurokawa, J.
  • Journal Title: J. Pharm. Sci. Volume: 134 Issue: 2 Pages: 75-85
  • DOI: 10.1016/j.jphs.2017.05.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Collagen Peptide Ingestion Alters Lipid Metabolism-Related Gene Expression and the Unfolded Protein Response in Mouse Liver. (2017)
  • Author(s): Tometsuka, C., Koyama, Y-I., Ishijima, T., Toyoda, T., Teranishi, M., Takehana, K., Abe, K., and Nakai, Y.
  • Journal Title: Br. J. Nutr. Volume: 117 Issue: 1 Pages: 1-11
  • DOI: 10.1017/s0007114516004384
  • NAID: 120006711683
  • Peer Reviewed / Open Access
• [Journal Article] Identification of BCL11B as a regulator of adipogenesis. (2016)
  • Author(s): Inoue, J., Ihara, Y., Tsukamoto, D., Yasumoto, K., Hashidume, T., Kamimura, K., Nakai, Y., Hirano, S., Shimizu, M., Kominami, R., and Sato R.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 32750-32750
  • DOI: 10.1038/srep32750
  • Peer Reviewed / Open Access
• [Journal Article] Single ingestion of soy β-conglycinin induces increased postprandial circulating FGF21 levels exerting beneficial health effects. (2016)
  • Author(s): Hashidume, T., Kato, A.,Tanaka, T., Miyoshi, S., Itoh, N., Nakata, R., Inoue, H., Oikawa, A., Nakai, Y., Shimizu, M., Inoue, J., and Sato R.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 28183-28183
  • DOI: 10.1038/srep28183
  • NAID: 120005774582
  • Peer Reviewed / Open Access
• [Journal Article] A high phosphorus diet affects lipid metabolism in rat liver: a DNA microarray analysis. (2016)
  • Author(s): Chun, S., Bamba, T., Suyama, T., Ishijima, T., Fukusaki, E., Abe, K., and Nakai, Y.
  • Journal Title: PLoS ONE Volume: 11 Issue: 5 Pages: e0155386-e0155386
  • DOI: 10.1371/journal.pone.0155386
  • Peer Reviewed / Open Access
• [Presentation] 貪食受容体による細胞競合調節機構 (Regulation of cell competition by engulfment receptors in Drosophila) (2019)
  • Author(s): 永長一茂, 野中さおり, 中井雄治, 中西義信
  • Organizer: 第92回日本生化学会大会
• [Presentation] 変異細胞の除去をターゲットとした潜在的ながん予防食品探索 (2019)
  • Author(s): 永長一茂, 福田覚, 泉ひかり
  • Organizer: 第26回日本がん予防学会学術大会
• [Presentation] 低・未利用海藻（イシモズク）を活用した共同研究・商品開発の事例紹介 (2019)
  • Author(s): 福田覚, 泉ひかり, 永長一茂, 嵯峨直恆
  • Organizer: 産学連携学会第17会大会
• [Presentation] The Development of High Throughput Screening System for Alzheimer's Disease-preventive Foods Using Drosophila (2018)
  • Author(s): Yuji Nakai, Kaz Nagaosa
  • Organizer: The Asia Pacific Nutrigenomics and Nutrigenetics Organisation 2018
  • Int'l Joint Research
• [Presentation] Findings of potentially cancer-preventive foods using Drosophila cell competition model (2018)
  • Author(s): Kaz Nagaosa, Yuji Nakai
  • Organizer: The Asia Pacific Nutrigenomics and Nutrigenetics Organisation 2018
  • Int'l Joint Research
• [Presentation] Appetite regulation of odors containing DMHF generated by the Maillard reaction (2018)
  • Author(s): Issei Yokoyama, Yuji Nakai, Yoshihiro Suzuki, Motoko Ohata, Yusuke Komiya, Keizo Arihara
  • Organizer: Institute of Food Technologists 18 Annual Meeting
  • Int'l Joint Research
• [Presentation] 幼若マウス心臓の形態・機能における性差について (2018)
  • Author(s): 児玉昌美, 橋口丈晃, 坂本多穂, 中井雄治, 山口賢彦, 黒川洵子
  • Organizer: 日本薬学会レギュラトリーサイエンス部会 第4回 次世代を担う若手のためのレギュラトリーサイエンスフォーラム
• [Presentation] カドミウム存在下で根へのグルタチオン添加に応答する遺伝子の発現解析および導管液と篩管液のメタボロミクス解析 (2018)
  • Author(s): 李 俊松, 及川 彰, 中井雄治, 中村進一, 大津直子
  • Organizer: 日本土壌肥料学会2018年度神奈川大会
• [Presentation] 細胞競合を利用した潜在的ながん予防食品のスクリーニング (2018)
  • Author(s): 永長一茂
  • Organizer: 3.がん予防学術大会2018高松 (第25回日本がん予防学会総会, 第41回日本がん免疫・分子免疫研究会総会)
• [Presentation] ショウジョウバエを用いたがん予防食品のスクリーニング (Screening of foods for cancer prevention by Drosophila). (2018)
  • Author(s): 永長一茂.
  • Organizer: 日本薬学会第138回年会
• [Presentation] リンゴおよびイシモズクによる細胞競合促進機構の解析 (Mechanisms of apple- and Ishimozuku-mediated regulation of cell competition). (2018)
  • Author(s): 永長一茂, 中井雄治.
  • Organizer: 日本農芸化学会2018年度名古屋大会
• [Presentation] メイラード反応生成香気（DMHF）曝露が脳内遺伝子発現に及ぼす影響 (Effect of maillard reaction odor (DMHF) exposure on brain gene expression). (2018)
  • Author(s): 横山壱成, 中井雄治, 鈴木喜博, 大畑素子, 小宮佑介, 有原圭三
  • Organizer: 日本農芸化学会2018年度名古屋大会
• [Presentation] 抑制性転写因子BCL11Bによる脂肪細胞分化および脂肪蓄積制御の解析 (2017)
  • Author(s): 井上順, 井原悠介, 塚本大介, 安本啓甫, 橋詰力, 中井雄治, 清水誠, 佐藤隆一郎
  • Organizer: 日本農芸化学会2017年度大会
  • Place of Presentation: 京都女子大（京都市）
  • Year and Date: 2017-03-17
• [Presentation] イシモズクがショウジョウバエ遺伝子発現に与える影響：DNAマイクロアレイ解析 (2017)
  • Author(s): 中井雄治, 福田覚, 永長一茂
  • Organizer: 日本農芸化学会2017年度大会
  • Place of Presentation: 京都女子大（京都市）
  • Year and Date: 2017-03-17
• [Presentation] Analysis of compound regulating both auxin and brassinosteroid signal transductions (2017)
  • Author(s): Tanaka-Jaroensanti, N., Yoon, J-M., Otani, M., Shirai, I., Park, S-H., Hayashi, K., Nakai, Y., Nakajima, M., Asami, T
  • Organizer: 第58回日本植物生理学会年会
  • Place of Presentation: 鹿児島大学郡元キャンパス（鹿児島市）
  • Year and Date: 2017-03-16
• [Presentation] 細胞競合における貪食受容体の役割 (Role of engulfment receptors in cell competition). (2017)
  • Author(s): 永長一茂, 西千恵子, 中井雄治, 野中さおり, 中西義信.
  • Organizer: 2017年度生命科学系学会合同年次大会 (第40回日本分子生物学会年会・第90回日本生化学会大会)
• [Presentation] 食細胞プライミングを導く転写因子 Tailless の同定 (Identification of transcription factor Tailless responsible for phagocyte priming). (2017)
  • Author(s): 野中さおり, 星ちはる, 金谷匠人, 宗野真衣, 中井雄治, 永長一茂, 中西義信.
  • Organizer: 2017年度生命科学系学会合同年次大会 (第40回日本分子生物学会年会・第90回日本生化学会大会)
• [Presentation] 転写因子Taillessを介した食細胞プライミング機構. (2017)
  • Author(s): 野中さおり, 金谷匠人, 星ちはる, 中井雄治, 永長一茂, 中西義信.
  • Organizer: 日本生化学会北陸支部第35回大会
• [Presentation] 高圧損傷した枯草菌栄養細胞における遺伝子発現解析. (2017)
  • Author(s): 稲岡隆史, Nguyen Huyen, 中井雄治, 森松和也, 木村啓太郎, 中浦嘉子, 山本和貴
  • Organizer: 2017年度生命科学系学会合同年次大会 (第40回日本分子生物学会年会・第90回日本生化学会大会)
• [Presentation] Old, but not obsolete - DNA microarray analysis for nutrigenomics (2016)
  • Author(s): Nakai, Y.
  • Organizer: The Asia Pacific Nutrigenomics and Nutrigenetics Organisation
  • Place of Presentation: Hilton Hotel in Gyeongju（大韓民国慶州市）
  • Year and Date: 2016-12-05
  • Int'l Joint Research / Invited
• [Presentation] DNA変異細胞の除去を促す食品成分の探索 (2016)
  • Author(s): 永長一茂, 前多隼人, 加藤陽治
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（仙台市）
  • Year and Date: 2016-09-25
• [Presentation] アポトーシス細胞貪食時の食細胞における遺伝子発現変動の機構と意義の解明. (2016)
  • Author(s): 野中さおり, 永長一茂, 中井雄治, 金谷匠人, 星ちはる, 中西義信.
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 東北大学川内キャンパス（仙台市）
  • Year and Date: 2016-09-25
• [Presentation] 高リン食摂取がラット肝臓における脂質代謝に及ぼす影響:DNAマイクロアレイによる解析 (2016)
  • Author(s): 千善宇, 馬場健史, 陶山達矢, 石島智子, 福崎英一郎, 阿部啓子, 中井雄治
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（仙台市）
  • Year and Date: 2016-09-25