Dopamine receptor D-2 activation suppresses the radiosensitizing effect of aripiprazole via activation of AMPK
- Authors
- Lee, Hyounji; Kang, Seongman; Sonn, Jong Kyung; Lim, Young-Bin
- Issue Date
- 9월-2019
- Publisher
- WILEY
- Keywords
- AMPK; breast cancer; dopamine receptor; drug repositioning; radiotherapy
- Citation
- FEBS OPEN BIO, v.9, no.9, pp.1580 - 1588
- Indexed
- SCIE
SCOPUS
- Journal Title
- FEBS OPEN BIO
- Volume
- 9
- Number
- 9
- Start Page
- 1580
- End Page
- 1588
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/63441
- DOI
- 10.1002/2211-5463.12699
- ISSN
- 2211-5463
- 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.
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Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
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