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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

1
Research Group of Natural Materials and Metabolism, Korea Food Research Institute, Wanju 55365, Korea
2
Department of Food Science and Engineering, Ewha Womans University, Seoul 03760, Korea
3
Department of Biochemistry, Collage of Medicine, Kosin University, Busan 49267, Korea
4
Research Group of Healthcare, Korea Food Research Institute, Wanju 55365, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Raffaele Velotta
Sensors 2021, 21(10), 3468; https://doi.org/10.3390/s21103468
Received: 27 April 2021 / Revised: 11 May 2021 / Accepted: 12 May 2021 / Published: 16 May 2021
(This article belongs to the Section Biosensors)
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. View Full-Text
Keywords: olfactory receptor; OR6M1; surface plasmon resonance; anthraquinone; MCF-7 breast cancer cell line; rutin olfactory receptor; OR6M1; surface plasmon resonance; anthraquinone; MCF-7 breast cancer cell line; rutin
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MDPI and ACS Style

Choi, Y.R.; Shim, J.; Park, J.-H.; Kim, Y.-S.; Kim, M.J. 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 2021, 21, 3468. https://doi.org/10.3390/s21103468

AMA Style

Choi YR, Shim J, Park J-H, Kim Y-S, Kim MJ. 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. 2021; 21(10):3468. https://doi.org/10.3390/s21103468

Chicago/Turabian Style

Choi, Yae Rim, Jaewon Shim, Jae-Ho Park, Young-Suk Kim, and Min Jung Kim. 2021. "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 21, no. 10: 3468. https://doi.org/10.3390/s21103468

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