Novel Molecular Targets of TAS2Rs on Inhibitory Expressions of VEGF

Objectives: Recently, bitter taste receptors (TAS2Rs) were reported to be expressed in extra-oral tissues as well as cancer cells, which are involved in cell migration and invasion through inhibition of cell adhesion molecule expression. Thus, the TAS2Rs are focus of attentions on molecular targets for cancer therapy. The purpose of current study is to investigate the expression of vascular endothelial growth factors (VEGF-A & VEGF-B) in human squamous carcinoma cell line-4 (HSC-4) employing bitter taste receptor agonists.
Methods: Human squamous carcinoma cell line-4 (HSC-4) were stimulated with TAS2R agonists; caffeine (1mM and 0.1mM), denatonium benzonate (1mM and 0.1mM), quinine (10mM and 1mM), and chlorpheniramine (1mM) for 0 and 8 hours. After stimulations, total RNA was extracted from the cells. The mRNA expressions were evaluated with reverse transcription real-time PCR.
Results: VEGF-A expressions in HSC-4 cells with stimulation of caffeine, denatonium benzonate, and quinine were significantly decreased to ~20% of control cells, while the VEGF-A expression in HSC-4 cells stimulated with chlorpheniramine was significantly increased to ~200% of control cells. VEGF-B expressions in HSC-4 cells stimulated with denatonium benzonate, quinine, and chlorpheniramine were significantly decreased to ~40% of control cells.
Conclusions: TAS2Rs stimulation conferred the decreased expression of VEGF-A and –B. Of note, both denatonium benzonate and quinine decreased the expression of both VEGFs. TAS2Rs would give rise to novel molecular targets for anti-angiogenesis therapy of cancer other than anti-VEGF and/or anti-VEGF receptor molecular target therapy.