Functional assays to define agonists and antagonists of the sigma-2 receptor

Chenbo Zeng, Justin M. Rothfuss, Jun Zhang, Suwanna Vangveravong, Wenhua Chu, Shihong Li, Zhude Tu, Jinbin Xu, Robert H. Mach

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

The sigma-2 receptor has been identified as a biomarker in proliferating tumors. To date there is no well-established functional assay for defining sigma-2 agonists and antagonists. Many sigma-2 ligands with diverse structures have been shown to induce cell death in a variety of cancer cells by triggering caspase-dependent and independent apoptosis. Therefore, in the current study, we used the cell viability assay and the caspase-3 activity assay to determine sigma-2 agonists and antagonists. Three classes of sigma-2 ligands developed in our laboratory were evaluated for their potency to induce cell death in two tumor cell lines, mouse breast cancer cell line EMT-6 and human melanoma cell line MDA-MB-435. The data showed that the EC50 values of the sigma-2 ligands using the cell viability assay ranged from 11.4 μM to >200 μM, which were comparable with the EC50 values obtained using the caspase-3 assay. Based on the cytotoxicity of a sigma-2 ligand relative to that of siramesine, a commonly accepted sigma-2 agonist, we have categorized our sigma-2 ligands into agonists, partial agonists, and antagonists. The establishment of functional assays for defining sigma-2 agonists and antagonists will facilitate functional characterization of sigma-2 receptor ligands and sigma-2 receptors.

Original languageEnglish
Pages (from-to)68-74
Number of pages7
JournalAnalytical Biochemistry
Volume448
Issue number1
DOIs
StatePublished - Mar 1 2014

Keywords

  • Agonist
  • Antagonist
  • Caspase-3
  • Cell viability
  • Functional assay
  • Sigma-2 receptor

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