2026-07-22T20:10:42Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/115842024-10-31T11:44:24Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Salvestrini, Valentina
author
Ciciarello, Marilena
author
Pensato, Valentina
author
Simonetti, Giorgia
author
Laginestra, Maria Antonella
author
Bruno, Samantha
author
Pazzaglia, Martina
author
De Marchi, Elena
author
Forte, Dorian
author
Orecchioni, Stefania
author
Martinelli, Giovanni
author
Bertolini, Francesco
author
Mendez-Ferrer, Simon
author
Adinolfi, Elena
author
Di Virgilio, Francesco
author
Cavo, Michele
author
Curti, Antonio
funder
Associazione Italiana Contro le Leucemie Linfomi e Mieloma
funder
Fatro Ibérica, S.L.
funder
Fabbri1905
funder
Regione Emilia-Romagna
funder
University of Bologna (Italia)
funder
Italian Association for Cancer Research
funder
American Society of Hematology
funder
Società Italiana di Ematologia
funder
Associazione Amici di Beat Leukemia Dr. Alessandro Cevenini ONLUS
funder
Bologna Brancch
funder
Fondazione Corrado e Bruno Maria Zaini
funder
Giuseppe Bigi Memorial Award
2021-01-08T08:54:52Z
2021-01-08T08:54:52Z
2020-07-24
Front Oncol. 2020; 10:1225
10.3389/fonc.2020.01225
2234-943X
Frontiers in oncology
32793492
http://hdl.handle.net/20.500.12105/11584
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.
eng
Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells.
journal article
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Data_Sheet_1_Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells.docx
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Data_Sheet_2_Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells.docx
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