Local anesthetics induce apoptosis in human thyroid cancer cells through the mitogen-activated protein kinase pathway

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Title:	Local anesthetics induce apoptosis in human thyroid cancer cells through the mitogen-activated protein kinase pathway
Authors:	許藝瓊;Chang, Yuan-Ching;Hsu, Yi-Chiung;Liu, Chien-Liang;Huang, Shih-Yuan;Hu, Meng-Chun;Cheng, Shih-Ping
Contributors:	生醫理工學院生醫科學與工程學系
Keywords:	Activation;Analysis;Anesthetics;Anesthetics, Local - pharmacology;Antineoplastic Agents - pharmacology;Apoptosis;Apoptosis - drug effects;BAX protein;Bcl-2 protein;Biology;Bupivacaine;Bupivacaine - pharmacology;c-Jun protein;Cancer;Cancer cells;Caspase;Caspase 3 - metabolism;Caspase 7 - metabolism;Caspase-3;Cell growth;Cell proliferation;Cell Proliferation - drug effects;Cleavage;Community colleges;Cytochrome;Cytochrome c;Cytochromes c - metabolism;Cytometry;Cytotoxicity;DNA microarrays;Drug Screening Assays, Antitumor;Enzyme Activation;Extracellular signal-regulated kinase;Flow cytometry;Gene Expression - drug effects;Humans;JNK protein;Kinases;Lesions;Lidocaine;Lidocaine - pharmacology;Local anesthesia;Local anesthetics;MAP kinase;MAP Kinase Signaling System - drug effects;Medicine;Membrane potential;Membrane Potential, Mitochondrial - drug effects;Mitochondria;Mitochondria - drug effects;Mitochondria - physiology;Mitogens;Necrosis;Pharmacology;Poly (ADP-Ribose) Polymerase-1;Poly(ADP-ribose) polymerase;Poly(ADP-ribose) Polymerases - metabolism;Protein kinase;Protein kinases;Proteins;Thyroid;Thyroid cancer;Thyroid gland;Thyroid Neoplasms;Transcription factors
Date:	2014-02-21
Issue Date:	2026-04-23 11:16:52 (UTC+8)
Publisher:	Public Library of Science;United States: Public Library of Science (PLoS)
Abstract:	摘要： Local anesthetics are frequently used in fine-needle aspiration of thyroid lesions and locoregional control of persistent or recurrent thyroid cancer. Recent evidence suggests that local anesthetics have a broad spectrum of effects including inhibition of cell proliferation and induction of apoptosis in neuronal and other types of cells. In this study, we demonstrated that treatment with lidocaine and bupivacaine resulted in decreased cell viability and colony formation of both 8505C and K1 cells in a dose-dependent manner. Lidocaine and bupivacaine induced apoptosis, and necrosis in high concentrations, as determined by flow cytometry. Lidocaine and bupivacaine caused disruption of mitochondrial membrane potential and release of cytochrome c, accompanied by activation of caspase 3 and 7, PARP cleavage, and induction of a higher ratio of Bax/Bcl-2. Based on microarray and pathway analysis, apoptosis is the prominent transcriptional change common to lidocaine and bupivacaine treatment. Furthermore, lidocaine and bupivacaine attenuated extracellular signal-regulated kinase 1/2 (ERK1/2) activity and induced activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase. Pharmacological inhibitors of MAPK/ERK kinase and p38 MAPK suppressed caspase 3 activation and PARP cleavage. Taken together, our results for the first time demonstrate the cytotoxic effects of local anesthetics on thyroid cancer cells and implicate the MAPK pathways as an important mechanism. Our findings have potential clinical relevance in that the use of local anesthetics may confer previously unrecognized benefits in the management of patients with thyroid cancer. 其他題名： PLoS One 出版者： United States: Public Library of Science (PLoS) 出版日期： 2014-02-21 出處： PLoS ONE, 2014-02, Vol.9 (2), p.e89563- 資源來源： Agricultural & Environmental Science Collection 版權： COPYRIGHT 2014 Public Library of Science 版權： 2014 Chang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 版權： 2014 Chang et al 2014 Chang et al 識別號： ISSN: 1932-6203 識別號： EISSN: 1932-6203 識別號： DOI: 10.1371/journal.pone.0089563 識別號： PMID: 24586874
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