Dopamine receptor D2 activation suppresses the radiosensitizing effect of aripiprazole via activation of AMPK

Hyounji Lee, Seong Man Kang, Jong Kyung Sonn, Young Bin Lim

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalFEBS Open Bio
DOIs
Publication statusPublished - 2019 Jan 1

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Radiation-Sensitizing Agents
Dopamine D2 Receptors
Adenosine Monophosphate
Protein Kinases
Chemical activation
MCF-7 Cells
A 769662
Drug Repositioning
Pharmaceutical Preparations
Phosphorylation
Radiation Tolerance
Aripiprazole
Cells
Breast Neoplasms

Keywords

  • AMPK
  • breast cancer
  • dopamine receptor
  • drug repositioning
  • radiotherapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Dopamine receptor D2 activation suppresses the radiosensitizing effect of aripiprazole via activation of AMPK. / Lee, Hyounji; Kang, Seong Man; Sonn, Jong Kyung; Lim, Young Bin.

In: FEBS Open Bio, 01.01.2019.

Research output: Contribution to journalArticle

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