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

Yae Rim Choi, Jaewon Shim, Jae Ho Park, Young Suk Kim, Min Jung Kim

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Article number3468
JournalSensors (Switzerland)
Volume21
Issue number10
DOIs
StatePublished - 2 May 2021

Bibliographical note

Funding Information:
Funding: This research was funded by the Main Research Program of the Korea Food Research Institute (KFRI) [E0170100-02, E0210601-01].

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Anthraquinone
  • MCF-7 breast cancer cell line
  • OR6M1
  • Olfactory receptor
  • Rutin
  • Surface plasmon resonance

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