Administration of local anesthetics, such as lidocaine, in the perioperative period improves outcomes of cancer patients. However, its precise mechanism is still unresolved. The growth of human cancer cell lines, including HeLa cells, are suppressed by lidocaine treatment. We identified that growth differentiation factor-15 (GDF-15) was commonly upregulated in lidocaine-treated cancer cell lines. GDF-15 is a divergent member of the transforming growth factor-β (TGF-β) superfamily and it is produced as an unprocessed pro-protein form and then cleaved to generate a mature form. In lidocaine-treated HeLa cells, increased production of GDF-15 in the endoplasmic reticulum (ER) was observed and unprocessed pro-protein form of GDF-15 was secreted extracellularly. Further, lidocaine induced apoptosis and apoptosis-inducible Tribbles homologue 3 (TRIB3) was also commonly upregulated in lidocaine-treated cancer cell lines. In addition, transcription factor C/EBP homologous protein (CHOP), which is a positive regulator of not only GDF-15 but TRIB3 was also induced by lidocaine. Lidocaine-induced growth suppression and apoptosis was suppressed by knockdown of GDF-15 or TRIB3 expression by small interference RNA (siRNA). These observations suggest that lidocaine suppresses the growth of cancer cells through increasing GDF-15 and TRIB3 expression, suggesting its potential application as cancer therapy.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411556 | PMC |
| http://dx.doi.org/10.1038/s41598-022-18572-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Activating the cGAS-STING Pathway by Manganese-Based Nanoparticles Combined with Platinum-Based Nanoparticles for Enhanced Ovarian Cancer Immunotherapy.
ACS Nano
January 2025
Department of Gynecology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P. R. China.
Recent research has demonstrated that activating the cGAS-STING pathway can enhance interferon production and the activation of T cells. A manganese complex, called TPA-Mn, was developed in this context. The reactive oxygen species (ROS)-sensitive nanoparticles (NPMn) loaded with TPA-Mn are developed.
View Article and Find Full Text PDFCirculating Tumor HPV-DNA in the Management of HPV-Positive Oropharyngeal Carcinoma: A Systematic Review.
Head Neck
January 2025
Department of Otolaryngology, University of California, Irvine, Chao Family Comprehensive Cancer Center, Orange, California, USA.
Purpose: Blood-borne, cell-free DNA has been proposed as a means of individualizing the management of human papillomavirus (HPV)-positive oropharyngeal carcinoma.
Methods And Materials: This study was designed based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. A comprehensive literature search of peer-reviewed publications from January 2013 to January 2024 was undertaken to identify prospective studies pertaining to the use of circulating HPV-DNA for oropharyngeal carcinoma.
DNA hypomethylation-related expression of hsa-miR-184 contributes to invasive growth of gonadotroph neuroendocrine pituitary tumors.
J Neuroendocrinol
January 2025
Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Gonadotroph neuroendocrine pituitary tumors are among the most common intracranial neoplasms. A notable proportion of these tumors is characterized by invasive growth which hampers the treatment results and worsens prognoses of patients. Increased hsa-miR-184 expression was observed in invasive as compared to non-invasive gonadotroph tumors.
View Article and Find Full Text PDFAdvances and applications of genome-edited animal models for severe combined immunodeficiency.
Zool Res
January 2025
Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong 510280, China. E-mail:
Severe combined immunodeficiency disease (SCID), characterized by profound immune system dysfunction, can lead to life-threatening infections and death. Animal models play a pivotal role in elucidating biological processes and advancing therapeutic strategies. Recent advances in gene-editing technologies, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), CRISPR/Cas9, and base editing, have significantly enhanced the generation of SCID models.
View Article and Find Full Text PDFNEDD4-Mediated GSNOR Degradation Aggravates Cardiac Hypertrophy and Dysfunction.
Circ Res
January 2025
Key Laboratory of Drug Targets and Translational Medicine for Cardio-cerebrovascular Diseases, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Jiangsu, China (X.T., X.L., X.S., Y. Zhang, Y. Zu, Q.F., L.H., S.S., F.C., L.X., Y.J.).
Background: The decrease in S-nitrosoglutathione reductase (GSNOR) leads to an elevation of S-nitrosylation, thereby exacerbating the progression of cardiomyopathy in response to hemodynamic stress. However, the mechanisms under GSNOR decrease remain unclear. Here, we identify NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) as a novel molecule that plays a crucial role in the pathogenesis of pressure overload-induced cardiac hypertrophy, by modulating GSNOR levels, thereby demonstrating significant therapeutic potential.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!