Potential role of the bitter taste receptor T2R14 in the prolonged survival and enhanced chemoresponsiveness induced by apigenin
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Potential role of the bitter taste receptor T2R14 in the prolonged survival and enhanced chemoresponsiveness induced by apigenin. / Stern, Louisa; Boehme, Lukas Fabian; Goetz, Mara Rebecca; Nitschke, Christine; Giannou, Anastasios; Zhang, Tao; Güngör, Cenap; Reeh, Matthias; Izbicki, Jakob Robert; Fliegert, Ralf; Hausen, Anne; Giese, Nathalia; Hackert, Thilo; Niv, Masha Y; Heinrich, Stefan; Gaida, Matthias Martin; Ghadban, Tarik.
in: INT J ONCOL, Jahrgang 62, Nr. 1, 6, 01.2023.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Potential role of the bitter taste receptor T2R14 in the prolonged survival and enhanced chemoresponsiveness induced by apigenin
AU - Stern, Louisa
AU - Boehme, Lukas Fabian
AU - Goetz, Mara Rebecca
AU - Nitschke, Christine
AU - Giannou, Anastasios
AU - Zhang, Tao
AU - Güngör, Cenap
AU - Reeh, Matthias
AU - Izbicki, Jakob Robert
AU - Fliegert, Ralf
AU - Hausen, Anne
AU - Giese, Nathalia
AU - Hackert, Thilo
AU - Niv, Masha Y
AU - Heinrich, Stefan
AU - Gaida, Matthias Martin
AU - Ghadban, Tarik
PY - 2023/1
Y1 - 2023/1
N2 - Bitter taste receptors (T2Rs) are G protein‑coupled receptors originally detected in the gustatory system. More recently, T2Rs have been shown to be expressed in extra‑oral cells eliciting non‑gustatory functions. Emerging evidence has suggested a potential role for T2R signaling in diverse pathophysiological conditions, including cancer. -The aim of the present study was to evaluate the expression of T2R14 in pancreatic ductal adenocarcinoma (PDAC) and to assess its involvement in the anticancer effects induced by apigenin, a natural ligand of T2R14. For this purpose, T2R14 expression was explored in PDAC tumor tissue and tumor‑derived cell lines. Using the cell lines expressing the highest levels of T2R14, its effects on chemoresponsiveness and migration upon activation with apigenin were investigated in vitro. To the best of our knowledge, the present study was the first to confirm the expression of the T2R family member T2R14 in PDAC. Patients with relatively high levels of T2R14 expression exhibited significantly prolonged overall survival compared with that of patients with low T2R14 expression. Furthermore, novel functions for apigenin were revealed; notably, apigenin was shown to elicit cytotoxic, anti‑migratory and chemosensitizing effects to 5‑fluoruracil (5‑FU) and to 5‑FU, leucovorin, irinotecan and oxaliplatin in pancreatic cancer cells. In conclusion, the present study extended the evidence for the anticancer effects of apigenin and strongly indicated the functional relevance of T2R14 in PDAC, even though their respective underlying pathways appear to be independent of each other.
AB - Bitter taste receptors (T2Rs) are G protein‑coupled receptors originally detected in the gustatory system. More recently, T2Rs have been shown to be expressed in extra‑oral cells eliciting non‑gustatory functions. Emerging evidence has suggested a potential role for T2R signaling in diverse pathophysiological conditions, including cancer. -The aim of the present study was to evaluate the expression of T2R14 in pancreatic ductal adenocarcinoma (PDAC) and to assess its involvement in the anticancer effects induced by apigenin, a natural ligand of T2R14. For this purpose, T2R14 expression was explored in PDAC tumor tissue and tumor‑derived cell lines. Using the cell lines expressing the highest levels of T2R14, its effects on chemoresponsiveness and migration upon activation with apigenin were investigated in vitro. To the best of our knowledge, the present study was the first to confirm the expression of the T2R family member T2R14 in PDAC. Patients with relatively high levels of T2R14 expression exhibited significantly prolonged overall survival compared with that of patients with low T2R14 expression. Furthermore, novel functions for apigenin were revealed; notably, apigenin was shown to elicit cytotoxic, anti‑migratory and chemosensitizing effects to 5‑fluoruracil (5‑FU) and to 5‑FU, leucovorin, irinotecan and oxaliplatin in pancreatic cancer cells. In conclusion, the present study extended the evidence for the anticancer effects of apigenin and strongly indicated the functional relevance of T2R14 in PDAC, even though their respective underlying pathways appear to be independent of each other.
KW - Humans
KW - Taste/physiology
KW - Apigenin/pharmacology
KW - Receptors, G-Protein-Coupled/genetics
KW - Signal Transduction
KW - Fluorouracil
U2 - 10.3892/ijo.2022.5454
DO - 10.3892/ijo.2022.5454
M3 - SCORING: Journal article
C2 - 36382671
VL - 62
JO - INT J ONCOL
JF - INT J ONCOL
SN - 1019-6439
IS - 1
M1 - 6
ER -