title: Label-Free Dynamic Mass Redistribution Reveals Low-Density, Prosurvivalα1B-Adrenergic Receptors in Human SW480 Colon Carcinoma Cells.
abstract: Small molecules that target the adrenergic family of G protein-coupled receptors (GPCRs) show promising therapeutic efficacy for the treatment of various cancers. In this study, we report that human colon cancer cell line SW480 expresses low-density functionalα1B-adrenergic receptors (ARs) as revealed by label-free dynamic mass redistribution (DMR) signaling technology and confirmed by quantitative reverse-transcriptase polymerase chain reaction analysis. Remarkably, although endogenousα1B-ARs are not detectable via either [3H]-prazosin-binding analysis or phosphoinositol hydrolysis assays, their activation leads to robust DMR and enhanced cell viability. We provide pharmacological evidence that stimulation ofα1B-ARs enhances SW480 cell viability without affecting proliferation, whereas stimulatingβ-ARs diminishes both viability and proliferation of SW480 cells. Our study illustrates the power of label-free DMR technology for identifying and characterizing low-density GPCRs in cells and suggests that drugs targeting bothα1B- andβ-ARs may represent valuable small-molecule therapeutics for the treatment of colon cancer.
authors.affiliation: Departments of Pharmacology (D.-A.H., J.-M.P., K.-S.L., C.X., N.S., C.H.) and Psychiatry and Behavioral Sciences (C.X., N.S.), University of Washington School of Medicine, Seattle, Washington.
authors.forename: Dorathy-Ann
authors.initials: DA
authors.lastname: Harris
authors.affiliation: Departments of Pharmacology (D.-A.H., J.-M.P., K.-S.L., C.X., N.S., C.H.) and Psychiatry and Behavioral Sciences (C.X., N.S.), University of Washington School of Medicine, Seattle, Washington.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Park
authors.affiliation: Departments of Pharmacology (D.-A.H., J.-M.P., K.-S.L., C.X., N.S., C.H.) and Psychiatry and Behavioral Sciences (C.X., N.S.), University of Washington School of Medicine, Seattle, Washington.
authors.forename: Kyung-Soon
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Departments of Pharmacology (D.-A.H., J.-M.P., K.-S.L., C.X., N.S., C.H.) and Psychiatry and Behavioral Sciences (C.X., N.S.), University of Washington School of Medicine, Seattle, Washington.
authors.forename: Cong
authors.initials: C
authors.lastname: Xu
authors.affiliation: Departments of Pharmacology (D.-A.H., J.-M.P., K.-S.L., C.X., N.S., C.H.) and Psychiatry and Behavioral Sciences (C.X., N.S.), University of Washington School of Medicine, Seattle, Washington.
authors.forename: Nephi
authors.initials: N
authors.lastname: Stella
authors.affiliation: Departments of Pharmacology (D.-A.H., J.-M.P., K.-S.L., C.X., N.S., C.H.) and Psychiatry and Behavioral Sciences (C.X., N.S.), University of Washington School of Medicine, Seattle, Washington chague@uw.edu.
authors.forename: Chris
authors.initials: C
authors.lastname: Hague
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D001702:Biopharmaceutics / Q000379:methods; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D055808:Drug Discovery; D006801:Humans; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013268:Stimulation, Chemical
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D043562:Receptors, G-Protein-Coupled