دورية أكاديمية
أعرض في EDS

Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14.

التفاصيل البيبلوغرافية
العنوان: Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14.
المؤلفون: Miller ZA; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Pharmacology Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Mueller A; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Kim T; Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Jolivert JF; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Ma RZ; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Muthuswami S; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Park A; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., McMahon DB; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Nead KT; Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Carey RM; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: ryan.carey@pennmedicine.upenn.edu., Lee RJ; Department of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: rjl@pennmedicine.upenn.edu.
المصدر: Cell reports [Cell Rep] 2023 Dec 26; Vol. 42 (12), pp. 113437. Date of Electronic Publication: 2023 Nov 22.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, c 2012-
مواضيع طبية MeSH: Papillomavirus Infections* , Head and Neck Neoplasms*/drug therapy, Humans ; Taste/physiology ; Receptors, G-Protein-Coupled/metabolism ; Squamous Cell Carcinoma of Head and Neck ; Lidocaine/pharmacology ; Quality of Life ; Apoptosis
مستخلص: Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs, and T2R activation can induce apoptosis. Lidocaine is a local anesthetic that also activates bitter taste receptor 14 (T2R14). Lidocaine has some anti-cancer effects, but the mechanisms are unclear. Here, we find that lidocaine causes intracellular Ca 2+ mobilization through activation of T2R14 in HNSCC cells. T2R14 activation with lidocaine depolarizes mitochondria, inhibits proliferation, and induces apoptosis. Concomitant with mitochondrial Ca 2+ influx, ROS production causes T2R14-dependent accumulation of poly-ubiquitinated proteins, suggesting that proteasome inhibition contributes to T2R14-induced apoptosis. Lidocaine may have therapeutic potential in HNSCCs as a topical gel or intratumor injection. In addition, we find that HPV-associated (HPV+) HNSCCs are associated with increased TAS2R14 expression. Lidocaine treatment may benefit these patients, warranting future clinical studies.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: R01 AI167971 United States AI NIAID NIH HHS; R01 DC016309 United States DC NIDCD NIH HHS; R21 DC020041 United States DC NIDCD NIH HHS; T32 GM008076 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: CP: Cancer; G-protein-coupled receptor; HPV+; anesthetic; apoptosis; bitter agonist; calcium; chemosensory receptor; cyclic-AMP; ubiquitin-proteasome system
المشرفين على المادة: 0 (Receptors, G-Protein-Coupled)
98PI200987 (Lidocaine)
تواريخ الأحداث: Date Created: 20231123 Date Completed: 20240101 Latest Revision: 20240207
رمز التحديث: 20240207
مُعرف محوري في PubMed: PMC10842818
DOI: 10.1016/j.celrep.2023.113437
PMID: 37995679
قاعدة البيانات: MEDLINE
الوصف
تدمد:2211-1247
DOI:10.1016/j.celrep.2023.113437