The chemosensory bitter taste receptors (T2Rs) are involved in proliferation and migration of breast cancer

Abstract

Background and ObjectiveBreast cancer is a very complex disease and involves interactions between many proteins. The human bitter taste receptors (T2Rs) are a group of 25 chemosensory proteins that belong to the G protein‐coupled receptor family. T2Rs mediate signal transduction in response to stimulation by a wide variety of bitter compounds. Earlier studies showed that bitter agonists such as quinidine and chloroquine triggered apoptosis in MCF‐7 breast cancer cells, and bitter melon extract inhibited breast cancer cell proliferation by modulating cell cycle regulatory genes and promoting apoptosis. However, the cell surface receptor (T2R) targets for these bitter compounds, and their expression and characterization in the cancer cells is not yet elucidated.MethodsTo delineate the expression profile of T2Rs in breast cancer MDA‐MB‐231 and MCF‐7 cells and non‐cancerous MCF‐10A cell line, quantitative PCR (qPCR) and flow cytometry analysis was done. Next, analysis of T2R4 and T2R49 in human breast cancer tissue panel was performed using qPCR array (Origene Inc.). Calcium mobilization experiment was pursued to analyze the functional response after stimulation of these cells using bitter compounds. Cell proliferation was pursued using MTT assay and migration analysis by RTCA xCELLigence cell system after stimulating the cells with T2R ligands.ResultsOur results suggest differential expression of T2Rs is breast cancer cells. Stimulation of endogenous T2Rs with bitter agonists leads to increase in intracellular calcium release. Breast cancer cells treated with T2R4 agonist show decrease in cell proliferation and migration compared to non‐cancerous cells. This effect was reversed upon T2R4 antagonist treatment. Furthermore, knockdown and/or overexpression studies of T2R4 in these cells suggest its role in inhibition of cell proliferation and migration of breast cancer cells.ConclusionsOur results suggest that T2Rs are involved in decrease of breast cancer cell proliferation and migration. Investigating the mechanistic role of these chemosensory T2Rs in breast cancer would aid in developing strategies to prevent and/or treat breast cancer.Support or Funding InformationThe Natural Sciences and Engineering Research Council of Canada (NSERC)