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Discovery of Orphan Olfactory Receptor 6M1 as a New Anticancer Target in MCF-7 Cells by a Combination of Surface Plasmon Resonance-Based and Cell-Based Systems

Authors :
Yae Rim Choi
Jaewon Shim
Jae-Ho Park
Young-Suk Kim
Min Jung Kim
Source :
Sensors, Vol 21, Iss 10, p 3468 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Olfactory receptors (ORs) account for 49% of all G protein-coupled receptors (GPCRs), which are important targets for drug discovery, and hence ORs may also be potential drug targets. Various ORs are expressed in breast cancer cells; however, most of them are orphan receptors, and thus, their functions are unknown. Herein, we present an experimental strategy using a surface plasmon resonance (SPR) system and a cell-based assay that allowed the identification of orphan OR6M1 as a new anticancer target in the MCF-7 breast cancer cell line. After the construction of stable OR6M1-expressing cells, the SPR-based screening of 108 chemicals for ligand activity was performed against OR6M1-expressing whole cells (primary screening) or membrane fragments (secondary screening). As a result, anthraquinone (AQ) and rutin were discovered to be new OR6M1 ligands. Based on calcium imaging in OR6M1-expressing Hana3A cells, AQ and rutin were classified as an OR6M1 agonist and antagonist, respectively. Cell viability and live/dead assays showed that AQ induced the death of MCF-7 cells, which was inhibited by rutin. Therefore, OR6M1 may be considered an anticancer target, and AQ may be considered a chemotherapeutic agent. This combined method can be widely used to discover the ligands and functions of other orphan GPCRs.

Details

Language :
English
ISSN :
14248220
Volume :
21
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Sensors
Publication Type :
Academic Journal
Accession number :
edsdoj.17bb00072cb1403bb7ca3154b49f90c3
Document Type :
article
Full Text :
https://doi.org/10.3390/s21103468