Related Experiment Video
Updated: Apr 15, 2026
Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
Bitter Taste Signalling via TAS2R43 Enhances Temozolomide Efficacy in Glioblastoma Cells
Ana R Costa1, Ana C Duarte1, Isabel Gonçalves1
1RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal.
Abstract:
Bitter taste receptors (TAS2Rs) are increasingly recognised as extraoral chemosensors that modulate diverse biological processes, including cancer cell behaviour and drug responsiveness. Many TAS2R ligands correspond to therapeutic compounds; however, their contribution to the response of brain tumours to chemotherapy remains unexplored. Here, we investigated whether the bitter taste signalling pathway is modulated by temozolomide (TMZ), the standard chemotherapeutic agent for glioblastoma, with an impact on treatment efficacy in glioblastoma cells. We show that TMZ elicits intracellular Ca2+ responses compatible with activation of G-protein-coupled receptor signalling and induces anti-proliferative and pro-apoptotic effects in multiple human glioblastoma cell lines. Pharmacological inhibition of bitter taste receptors, as well as genetic silencing of the taste transduction G protein GNAT3, significantly attenuated TMZ-induced cytotoxicity, suggesting that bitter taste signalling is involved in this process. In silico ligand prediction combined with receptor expression profiling identified TAS2R43 as a candidate modulator of these effects, and TAS2R43 knockdown markedly reduced TMZ-induced loss of cell viability and apoptosis. Moreover, TMZ enhanced intracellular accumulation of the ABC transporter substrate doxorubicin, suggesting modulation of multidrug efflux mechanisms. Collectively, our findings identify TAS2R43 as a potential biomarker that warrants further validation to improve responses to TMZ and other ABC transporter-limited anticancer drugs.
Insights
Bitter taste receptors (TAS2Rs) modulate glioblastoma cell response to temozolomide (TMZ) chemotherapy. Targeting TAS2R43 may improve treatment efficacy for brain tumors.
Area of Science:
- Molecular Biology
- Cancer Research
- Neuro-oncology
Background:
- Bitter taste receptors (TAS2Rs) function as extraoral chemosensors influencing cancer cell behavior and drug response.
- The role of TAS2Rs in brain tumor response to chemotherapy, specifically glioblastoma's response to temozolomide (TMZ), is largely unexplored.
Purpose of the Study:
- To investigate if the bitter taste signaling pathway is modulated by temozolomide (TMZ) in glioblastoma cells.
- To determine the impact of this modulation on glioblastoma treatment efficacy.
Main Methods:
- Assessed intracellular Ca2+ responses to TMZ in glioblastoma cells.
- Utilized pharmacological inhibition and genetic silencing (GNAT3, TAS2R43) to evaluate the role of bitter taste signaling.
- Employed in silico ligand prediction and receptor expression profiling to identify candidate TAS2Rs.
- Investigated TMZ's effect on doxorubicin accumulation via ABC transporters.
Main Results:
- TMZ induced anti-proliferative and pro-apoptotic effects in glioblastoma cells, linked to G-protein-coupled receptor signaling.
- Inhibition or silencing of TAS2Rs and GNAT3 attenuated TMZ-induced cytotoxicity.
- TAS2R43 was identified as a key modulator; its knockdown significantly reduced TMZ's anti-cancer effects.
- TMZ enhanced doxorubicin accumulation, suggesting modulation of multidrug efflux mechanisms.
Conclusions:
- Bitter taste signaling, particularly involving TAS2R43, plays a significant role in glioblastoma cell response to TMZ.
- TAS2R43 may serve as a potential biomarker for predicting response to TMZ.
- Targeting TAS2R43 could offer a strategy to enhance the efficacy of TMZ and other anticancer drugs limited by ABC transporter activity.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:27Tumor Immunotherapy
01:24The Physiology of Taste