Elucidation of the mechanism of maintenance and fluctuation of circadian rhythm by anticancer drugs focusing on NADP(H)

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K14947
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: University of Toyama
• Principal Investigator: Okazaki Fumiyasu 富山大学, 学術研究部薬学・和漢系, 助教 (20610348)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 時間薬理 / 体内時計

Outline of Final Research Achievements

Sulfasalazine, an xCT inhibitor, has recently attracted attention as a potential novel anticancer drug that is able to affect cancer cells and drug-resistant cancer cells, such as cancer stem–like cells (CSC). However, previous reports suggested that anticancer drugs change the circadian rhythm, and elucidation of the mechanism is an important theme for clinical use of chronomodulated chemotherapy. In this study, it was confirmed that sulfasalazine oscillates the 24-hour variations of clock genes in culture cells. In addition, circadian rhythm is maintained depending on dosing time of sulfasalazine, and that NADPH/NADP is involved. These results of this study may be considered to be important findings for clinical use of chronomodulated chemotherapy.

Free Research Field

時間薬理

Academic Significance and Societal Importance of the Research Achievements

スルファサラジンを用いた時間薬物療法は、スルファサラジンの抗腫瘍効果を増大させるだけでなく、他の抗がん剤の抗腫瘍効果を増大させる。がん化学療法では、一般的に複数の薬剤を併用することから、日周リズムの維持・変動のメカニズムや日周リズムが回復するまでの休薬期間の解明は、抗がん剤の投薬スケジュールを決定する上で重要なエビデンスになると考えられる。また、日周リズムの異常は、鬱や代謝異常、循環器異常など様々な疾患の原因になることから、今後抗がん剤投薬によって生じる副作用のメカニズム解明にもつながると期待される。