Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells
Authors
Salvestrini, Valentina
Ciciarello, Marilena
Pensato, Valentina
Simonetti, Giorgia
Laginestra, Maria Antonella
Bruno, Samantha
Pazzaglia, Martina
De Marchi, Elena
Forte, Dorian
Orecchioni, Stefania
Martinelli, Giovanni
Bertolini, Francesco
Méndez-Ferrer, Simon
Adinolfi, Elena
Di Virgilio, Francesco
Cavo, Michele
Curti, Antonio
Publication Date
2020-07-24Journal Title
Frontiers in Oncology
Publisher
Frontiers Media S.A.
Volume
10
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Salvestrini, V., Ciciarello, M., Pensato, V., Simonetti, G., Laginestra, M. A., Bruno, S., Pazzaglia, M., et al. (2020). Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells. Frontiers in Oncology, 10 https://doi.org/10.3389/fonc.2020.01225
Abstract
The contribution of cell-extrinsic factors in Acute Myeloid Leukemia (AML) generation and persistence has gained interest. Bitter taste receptors (TAS2Rs) are G protein-coupled receptors known for their primary role as a central warning signal to induce aversion toward noxious or harmful substances. Nevertheless, the increasing amount of evidence about their extra-oral localization has suggested a wider function in sensing microenvironment, also in cancer settings. In this study, we found that AML cells express functional TAS2Rs. We also highlighted a significant association between the modulation of some TAS2Rs and the poor-prognosis AML groups, i.e., TP53- and TET2-mutated, supporting a potential role of TAS2Rs in AML cell biology. Gene expression profile analysis showed that TAS2R activation with the prototypical agonist, denatonium benzoate, significantly modulated a number of genes involved in relevant AML cellular processes. Functional assay substantiated molecular data and indicated that denatonium reduced AML cell proliferation by inducing cell cycle arrest in G0/G1 phase or induced apoptosis via caspase cascade activation. Moreover, denatonium exposure impaired AML cell motility and migratory capacity, and inhibited cellular respiration by decreasing glucose uptake and oxidative phosphorylation. In conclusion, our results in AML cells expand the observation of cancer TAS2R expression to the setting of hematological neoplasms and shed light on a role of TAS2Rs in the extrinsic regulation of leukemia cell functions.
Keywords
Oncology, acute myeloid leukemia, bitter taste receptors, denatonium benzoate, bone marrow microenvironment, bitter compounds
Identifiers
External DOI: https://doi.org/10.3389/fonc.2020.01225
This record's URL: https://www.repository.cam.ac.uk/handle/1810/308870
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/