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
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 functi...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Sensors |
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| Online Access: | https://www.mdpi.com/1424-8220/21/10/3468 |
| _version_ | 1797533859362897920 |
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| author | Yae Rim Choi Jaewon Shim Jae-Ho Park Young-Suk Kim Min Jung Kim |
| author_facet | Yae Rim Choi Jaewon Shim Jae-Ho Park Young-Suk Kim Min Jung Kim |
| author_sort | Yae Rim Choi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T11:21:38Z |
| format | Article |
| id | doaj.art-17bb00072cb1403bb7ca3154b49f90c3 |
| institution | Directory Open Access Journal |
| issn | 1424-8220 |
| language | English |
| last_indexed | 2024-03-10T11:21:38Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Sensors |
| spelling | doaj.art-17bb00072cb1403bb7ca3154b49f90c32023-11-21T19:58:07ZengMDPI AGSensors1424-82202021-05-012110346810.3390/s21103468Discovery 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 SystemsYae Rim Choi0Jaewon Shim1Jae-Ho Park2Young-Suk Kim3Min Jung Kim4Research Group of Natural Materials and Metabolism, Korea Food Research Institute, Wanju 55365, KoreaResearch Group of Natural Materials and Metabolism, Korea Food Research Institute, Wanju 55365, KoreaResearch Group of Healthcare, Korea Food Research Institute, Wanju 55365, KoreaDepartment of Food Science and Engineering, Ewha Womans University, Seoul 03760, KoreaResearch Group of Natural Materials and Metabolism, Korea Food Research Institute, Wanju 55365, KoreaOlfactory 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.https://www.mdpi.com/1424-8220/21/10/3468olfactory receptorOR6M1surface plasmon resonanceanthraquinoneMCF-7 breast cancer cell linerutin |
| spellingShingle | Yae Rim Choi Jaewon Shim Jae-Ho Park Young-Suk Kim Min Jung Kim 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 Sensors olfactory receptor OR6M1 surface plasmon resonance anthraquinone MCF-7 breast cancer cell line rutin |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | olfactory receptor OR6M1 surface plasmon resonance anthraquinone MCF-7 breast cancer cell line rutin |
| url | https://www.mdpi.com/1424-8220/21/10/3468 |
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