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 11.4μM to >200μM, 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 characterizatio...Continue Reading
References
May 24, 1995·European Journal of Pharmacology·W D BowenK C Rice
May 26, 1995·Journal of Medicinal Chemistry·J PerregaardC Sánchez
Jul 14, 1995·European Journal of Pharmacology·R R MatsumotoB R De Costa
Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·M HannerH Glossmann
Mar 30, 1999·Life Sciences·R H MachS R Childers
Mar 29, 2000·British Journal of Cancer·K T WheelerR H Mach
Jul 4, 2001·Biochemical Pharmacology·J Mei, G W Pasternak
Dec 20, 2003·Bioorganic & Medicinal Chemistry Letters·Robert H MachRobert R Luedtke
Mar 23, 2005·Nature Methods·Monika SuchanekChristoph Thiele
Oct 6, 2005·Cancer Research·Marie Stampe OstenfeldMarja Jäättelä
Nov 18, 2005·European Journal of Pharmacology·Jinbin XuRobert H Mach
Mar 4, 2006·Endocrinology·J J PelusoMartin Wehling
Jul 14, 2006·Bioorganic & Medicinal Chemistry·Suwanna VangveravongRobert H Mach
Feb 6, 2007·Cell Metabolism·Adam L HughesPeter J Espenshade
Jun 21, 2007·Journal of Medicinal Chemistry·Zhude TuRobert H Mach
Jun 23, 2007·The Journal of Steroid Biochemistry and Molecular Biology·Michael A Cahill
Jul 17, 2007·Molecular Cancer·Hiroyuki KashiwagiWilliam G Hawkins
Jan 3, 2009·Bioorganic & Medicinal Chemistry·Wenhua ChuRobert H Mach
Jul 22, 2009·Pharmacology & Therapeutics·Tangui Maurice, Tsung-Ping Su
Oct 22, 2009·Journal of Medicinal Chemistry·Francesco BerardiRoberto Perrone
Jun 12, 2010·The Journal of Biological Chemistry·Ikhlas S AhmedRolf J Craven
Mar 8, 2011·Bioorganic & Medicinal Chemistry·Kuo-Hsien FanSusan Z Lever
Jul 7, 2011·Nature Communications·Jinbin XuRobert H Mach
Jan 19, 2012·British Journal of Cancer·C ZengR H Mach
Feb 1, 2012·Current Pharmaceutical Design·Carmen AbateFrancesco Berardi
Oct 13, 2012·Biochemical Pharmacology·Jane SpirkoskiGunnar Pejler
Jun 6, 2013·Journal of Medicinal Chemistry·Robert H MachWilliam G Hawkins
Citations
Nov 18, 2015·The Journal of Pharmacology and Experimental Therapeutics·Hilary NicholsonWayne D Bowen
Dec 26, 2015·Nuclear Medicine and Biology·Mehran MakvandiDaniel A Pryma
Oct 11, 2015·Biochemical and Biophysical Research Communications·Mehran MakvandiRobert H Mach
May 18, 2016·The Journal of Pharmacology and Experimental Therapeutics·Jonathan L KatzChristopher R McCurdy
Jul 13, 2016·Future Medicinal Chemistry·Martín EstradaMaría Isabel Rodríguez-Franco
Oct 30, 2016·European Journal of Medicinal Chemistry·Marta RuiSimona Collina
Jan 5, 2017·Expert Opinion on Therapeutic Patents·Simona CollinaAnna Tesei
Jun 24, 2017·ACS Chemical Neuroscience·James J SahnTheodore J Price
Sep 25, 2017·ChemMedChem·Silvia FranchiniLivio Brasili
Dec 12, 2018·The Journal of Pharmacology and Experimental Therapeutics·Hilary E NicholsonWayne D Bowen
Jun 3, 2015·The Journal of Pharmacology and Experimental Therapeutics·Hilary NicholsonWayne D Bowen
Aug 5, 2020·Expert Opinion on Therapeutic Targets·James Michael BrimsonTewin Tencomnao
Nov 7, 2019·Frontiers in Pharmacology·Halley M OyerFelix J Kim
Nov 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kai YangTaolei Sun
Oct 14, 2020·European Journal of Medicinal Chemistry·Xiao-Yang XieYun-Sheng Huang
Oct 3, 2020·Bioorganic & Medicinal Chemistry·Benjamin SchinorGünter Haufe
Mar 30, 2017·Biochemical and Biophysical Research Communications·Elizabeth S McDonaldChenbo Zeng
Oct 13, 2020·Neuropharmacology·Wen-Hui MaYun-Sheng Huang
May 24, 2021·Neuropharmacology·Kelsey C NorthAlex M Dopico
Jun 3, 2021·Journal of Medicinal Chemistry·Antonino N FallicaSebastiano Intagliata
Jun 3, 2021·International Journal of Molecular Sciences·Rareş-Petru MoldovanWinnie Deuther-Conrad
Jun 19, 2021·European Journal of Pharmacology·Cheri Z LiuWayne D Bowen
Apr 25, 2017·ACS Medicinal Chemistry Letters·James J SahnStephen F Martin