글로벌 연구동향
방사선생물학
- 2019년 09월호
[FEBS Open Bio.] Dopamine receptor D2 activation suppresses the radiosensitizing effect of aripiprazole via activation of AMPK.KIRAMS /이현지, 임영빈*
- 출처
- FEBS Open Bio.
- 등재일
- 2019 Jul 13. doi: 10.1002/2211-5463.12699. [Epub a
- 저널이슈번호
- 내용
Abstract
Drug repositioning has garnered attention as an alternative strategy to the discovery and development of novel anticancer drug candidates. In this study, we screened 321 FDA-approved drugs against nonirradiated and irradiated MCF-7 cells, revealing that aripiprazole, a dopamine receptor D2 (D2R) partial agonist, enhances the radiosensitivity of MCF-7 cells. Unexpectedly, D2R-selective antagonist treatment significantly enhanced the radiosensitizing effects of aripiprazole and prevented aripiprazole-induced 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. Direct AMPK activation with A769662 treatment blunted the radiosensitizing effects of aripiprazole. These results indicate that aripiprazole has potential as a radiosensitizing drug. Furthermore, prevention of D2R/AMPK activation might enhance these anticancer effects of aripiprazole in breast cancer cells.
Author informationLee H1, Kang S2, Sonn JK3, Lim YB1.
1
Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
2
Division of Life Science, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
3
Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Korea.
- 키워드
- AMPK; breast cancer; dopamine receptor; drug repositioning; radiotherapy
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