Functional assays to define agonists and antagonists of the sigma-2 receptor |
| |
Authors: | Chenbo Zeng Justin M Rothfuss Jun Zhang Suwanna Vangveravong Wenhua Chu Shihong Li Zhude Tu Jinbin Xu Robert H Mach |
| |
Institution: | 1. Department of Radiology, Division of Radiological Sciences, Washington University School of Medicine, 510 S. Kingshighway Blvd., St. Louis, MO 63110, USA;2. Department of Cell Biology and Physiology, Washington University School of Medicine, 510 S. Kingshighway Blvd., St. Louis, MO 63110, USA;3. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 510 S. Kingshighway Blvd., St. Louis, MO 63110, USA |
| |
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. |
| |
Keywords: | Sigma-2 receptor Agonist Antagonist Caspase-3 Cell viability Functional assay |
本文献已被 ScienceDirect 等数据库收录! |
|