The regulation of DNA damage response by foods or its ingredients

• Project/Area Number: 24580203
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Nigata University of Phermacy and Applied Life Sciences
• Principal Investigator: NISHIDA HIROSHI 新潟薬科大学, 応用生物科学部, 教授 (60322541)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: ATM / ATR / Checkpoint / food extracts / flavonoid / gomisin-N / チェックポイント / 癌治療 / 放射線 / 抗癌剤 / スクアレン / 柿葉 / DNA損傷 / 重粒子線 / SchsandrinB / 抗がん剤

Outline of Final Research Achievements

ATM and ATR protein kinases play a crucial role in cellular DNA damage responses. The inhibition of these kinases and related molecules lead to an abolishment of one such signal pathways termed as ”checkpoints”. It is expected that the discovery of checkpoint modulator will be an effective assistance of anti-cancer therapy. We discovered several candidates from foods including resourses of traditional medicines. Gomisin-N and Persimmon leaf foavonols (PLF) inhibited ATR and ATM in vivo and in vitro, respectivly. The inhibitory effect of PLF was observed in xenograft mice which irradiated with heavy ion carbon beam. Addition, we discovered some food stuffs which inhibit tumor cell growth such as 3,4-dihydroxybenzalacetone, feruic acid/gamma-tocotorienol and phosphatidylcholine peroxide. Here, we revealed anti-cancer effects of ingrients of foods, and clarified detailed mechanisms of intracellular signal regulation.

Research Products

• [Journal Article] Metabolism and cytotoxic effects of phosphatidylcholine hydroperoxide in human hepatoma HepG2 cells (2015)
  • Author(s): Y. Suzuki, K. Nakagawa, S. Kato, N. Tatewaki, S. Mizuochi, J. Ito, T. Eitsuka, H. Nishida, T. Miyazawa
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 458 Issue: 4 Pages: 920-927
  • DOI: 10.1016/j.bbrc.2015.02.063
  • Peer Reviewed / Open Access
• [Journal Article] Synergistic inhibition of cancer cell proliferation with a combination of δ-tocotrienol and ferulic acid. (2014)
  • Author(s): Eitsuka T, Tatewaki N, Nishida H, Kurata T, Nakagawa K, Miyazawa T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 453 Issue: 3 Pages: 606-611
  • DOI: 10.1016/j.bbrc.2014.09.126
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of acute and chronic boysenberry intake on blood pressure and endothelial function in spontaneous hypertensive rats. (2014)
  • Author(s): Matsushima A, Furuuchi R, Shirai M, Nagai S, Yokoyama T, Nishida H, Hirayama M
  • Journal Title: J Nutr Sci Vitaminol (Tokyo) Volume: 60 Pages: 43-51
  • NAID: 130003393764
  • Peer Reviewed / Open Access
• [Journal Article] Persimmon Leaf Flavonols Enhance the Anti-Cancer Effect of Heavy Ion Radiotherapy on Murine Xenograft Tumors (2013)
  • Author(s): Kawakami K, Nishida H, Tatewaki N, Eguchi-Kasai E, Anzai K, Eitsuka T, Konishi T, Hirayama M
  • Journal Title: Journal of Cancer Therapy Volume: 4 Issue: 07 Pages: 1150-1157
  • DOI: 10.4236/jct.2013.47133
  • Peer Reviewed
• [Presentation] Squalene inhibits inflammation in tumor transplanted mice (2014)
  • Author(s): Tatewaki N, Eitsuka T, Nishida H
  • Organizer: Society of Free Radical Biology & Medicine
  • Place of Presentation: Seattle Convention Center
  • Year and Date: 2014-11-19 – 2014-11-23
• [Presentation] The mechanisms of Wip1 phosphatase expression-induced by Squalene in cancer cells (2013)
  • Author(s): Tatewaki N, Eitsuka T, Konishi T, Nishida H
  • Organizer: American Society for Cell Biology
  • Place of Presentation: New Orleans Convention Center
• [Patent(Industrial Property Rights)] 抗癌剤 (2014)
  • Inventor(s): 赤井 昭二、青島 啓太、西田 浩志 ほか３名
  • Industrial Property Rights Holder: 赤井 昭二、青島 啓太、西田 浩志 ほか３名
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-142432
  • Filing Date: 2014-07-10