Denatonium as a bitter taste receptor agonist modifies transcriptomic profile and functions of acute myeloid leukemia cells

Bitter taste receptors (T2Rs) are typical G-protein coupled receptors expressed in various tissue where they are involved in the regulation of physiological processes, thus suggesting a wider function in sensing microenvironment. We analyzed their expression and role in acute myeloid leukemia (AML). AML cells express functional T2Rs and their stimulation with the agonist, denatonium benzoate, substantially modified the AML cell transcriptomic profile and functions. GEP analysis identified relevant cellular processes affected by denatonium treatment in AML, including cell cycle, survival, migration and metabolism. More precisely, T2R activation reduced proliferation by inducing cell cycle arrest in G0/G1 phase or induced apoptosis via caspase cascade activation; impaired AML cell motility and migratory capacity; inhibited cellular respiration by decreasing glucose uptake and oxidative phosphorylation. THP-1 and OCI-AML3 cell lines and primary AML cells treated with denatonium (or vehicle) for 24h were used for RNA extraction and hybridization on Affymetrix microarrays.