Cyclosporine A and bromocriptine attenuate cell death mediated by intracellular calcium mobilization

In Ki Kim, So Jung Park, Jhang Ho Park, Seung Ho Lee, Sung Eun Hong, John C. Reed

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


To identify the novel inhibitors of endoplasmic reticulum stress-induced cell death, we performed a high throughput assay with a chemical library containing a total of 3,280 bioactive small molecules. Cyclosporine A and bromocriptine were identified as potent inhibitors of thapsigargiin-induced cell death (cut-off at 4σ standard score). However, U74389G, the potent inhibitor of lipid peroxidation had lower activity in inhibiting cell death. The inhibition effect of cyclosporine A and bromocriptine was specific for only thapsigargin-induced cell death. The mechanism of inhibition by these compounds was identified as modification of the expression of glucose regulated protein-78 (GRP-78/Bip) and inhibition of phosphorylation of p38 mitogen activated protein kinase (MAPK). However, these compounds did not inhibit the same events triggered by tunicamycin, which was in agreement with the cell survival data. We suggest that the induction of protective unfolded protein response by these compounds confers resistance to cell death. In summary, we identified compounds that may provide insights on cell death mechanisms stimulated by ER stress.

Original languageEnglish
Pages (from-to)482-487
Number of pages6
JournalBMB Reports
Issue number8
StatePublished - Aug 2012


  • Bromocriptine
  • Calcium mobilization
  • Cyclosporine A
  • Endoplasmic reticulum stress


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