Construction of cancer chronotherapy by manipulation of biological clock via mTOR signal pathway.

• Project/Area Number: 15K19167
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied pharmacology
• Research Institution: Daiichi University, College of Pharmaceutical Sciences
• Principal Investigator: Okazaki Hiroyuki 第一薬科大学, 薬学部, 助教 (50734125)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: mTOR / がん / 時計遺伝子 / 体内時計 / 薬物療法

Outline of Final Research Achievements

To elucidate the interaction between the diurnal rhythm of mTOR signal and the circadian clock system, and to find a new therapeutic strategy for cancer and other mTOR related diseases by manipulating mTOR diurnal rhythm, this research was carried out. Two reports on cancer proliferation and biological clock mechanism were published. I also clarified a part of the interaction of the effect of the diurnal rhythm of the mTOR signal and its inhibition on the internal clock mechanism. These findings will find the possibility of application as a new target on the influence of mTOR signal in elucidation and treatment of various diseases such as cancer.

Research Products

• [Journal Article] Cannabidiolic acid-mediated selective down-regulation of c-fos in highly aggressive breast cancer MDA-MB-231 cells: possible involvement of its down-regulation in the abrogation of aggressiveness. (2016)
  • Author(s): Takeda S, Himeno T, Kakizoe K, Okazaki H, Okada T, Watanabe K, Aramaki H
  • Journal Title: Journal of natural medicines Volume: 71 Issue: 1 Pages: 286-291
  • DOI: 10.1007/s11418-016-1030-0
  • NAID: 40021062820
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Circadian Clock in a Mouse Colon Tumor Regulates Intracellular Iron Levels to Promote Tumor Progression. (2016)
  • Author(s): Okazaki F, Matsunaga N, Okazaki H, Azuma H, Hamamura K, Tsuruta A, Tsurudome Y, Ogino T, Hara Y, Suzuki T, Hyodo K, Ishihara H, Kikuchi H, To H, Aramaki H, Koyanagi S, Ohdo S
  • Journal Title: The Journal of biological chemistry Volume: 291 Issue: 13 Pages: 7017-7028
  • DOI: 10.1074/jbc.m115.713412
  • Peer Reviewed / Open Access / Acknowledgement Compliant