Adhesion G-protein-coupled receptor (GPCR) and Triple-negative breast cancer (TNBC): A new perspective for the therapeutic effect of GPR116 in TNBC

Research on finding a novel molecular target for the treatment of triple-negative breast cancer (TNBC) is getting more attention nowadays because of the complex nature of the cancer and issues with the existing therapeutic strategies. G-protein-coupled receptor116 (GPCR116) is an orphan adhesion receptor known for its role in cell invasion and promotion of metastasis. In this study, GPR116 was chosen as the target and the effect of quercetin and doxorubicin on the expression of GPR116 was examined. MDA-MB 231 cells were used to evaluate the effect of quercetin and doxorubicin on cell proliferation, invasion, and apoptosis assays. Expression of GPR116 in mRNA and protein levels were evaluated by qRT-PCR and Western blotting, respectively. Quercetin inhibited MDA-MB 231 cell proliferation similar to the standard drug doxorubicin and a cell cycle analysis study disclosed that quercetin leads to cell death via apoptosis and doxorubicin induces more necrotic effect. These ligand candidates inhibit the expression of GPR116 in mRNA and protein levels. qRT-PCR results showed that quercetin efficiently inhibits the expression of GPR116 than doxorubicin and 2-fold variations were observed between quercetin and doxorubicin. Western blotting results also found the selected ligands effectively inhibit the GPRR116 protein. Tran swell migration study showed quercetin inhibits migration effectively compared with untreated cells. Inhibition of cell migration may be due to the downregulation of GPR116 expression in treated cells. Thus, the findings of this experimental study revealed that quercetin and doxorubicin could target the GPR116 in the treatment of TNBC.