Abstract
Non-small cell lung carcinoma (NSCLC) is the leading type of lung cancer; smoking is a documented risk factor. Nicotinic acetylcholine receptor (nAChR)-mediated intracellular signaling in response to nicotine has recently been implicated in the growth regulation of NSCLC. In the current study nude mice carrying xenografts of the human lung NSCLC cell lines NCI-H322 or NCI-H441 were used as animal models. Nicotine administration and gamma aminobutyric acid (GABA) treatment lasted for 30 days. Catecholamines, cortisol, GABA, and cAMP were analyzed in blood and tumor tissues by immunoassays. Expression of nicotinic receptors and effector proteins in the xenografts was assessed by Western blotting. Our data indicate that nicotine stimulated the growth of NSCLC xenografts via modulation of nAChR upregulation and activation of cAMP signaling. The nicotine-treated group showed an enhanced level of stress neurotransmitters and second messenger cAMP in serum, blood cellular fraction, and xenograft tissues. Activation of critical proteins in the oncogenic pathway, including CREB, ERK, Akt, and Src, and upregulation of α-4 and α-7 subunits of nAChR provided mechanistic insight for the observed stimulatory effect of nicotine. Interestingly, GABA, being an antagonist to cAMP signaling, showed a promising intervention by reversing the stimulatory effect of nicotine on cancer growth and all signaling pathways. GABA has potential to lower the risk of NSCLC among smokers and could be used to enhance the clinical outcome of standard cancer intervention strategies.
Keywords: GABA, intervention study, NSCLC, nAChR drug target, nicotine, smoking, xenografts, adenocarcinoma, cyclic adenosine monophosphate, nicotinic acetylcholine receptor, glutamic acid decarboxylase, bicinchoninic acid
Current Cancer Drug Targets
Title: Gamma-Amino Butyric Acid Inhibits the Nicotine-Imposed Stimulatory Challenge in Xenograft Models of Non-Small Cell Lung Carcinoma
Volume: 12 Issue: 2
Author(s): H. A.N. Al-Wadei, M. H. Al-Wadei, M. F. Ullah and H. M. Schuller
Affiliation:
Keywords: GABA, intervention study, NSCLC, nAChR drug target, nicotine, smoking, xenografts, adenocarcinoma, cyclic adenosine monophosphate, nicotinic acetylcholine receptor, glutamic acid decarboxylase, bicinchoninic acid
Abstract: Non-small cell lung carcinoma (NSCLC) is the leading type of lung cancer; smoking is a documented risk factor. Nicotinic acetylcholine receptor (nAChR)-mediated intracellular signaling in response to nicotine has recently been implicated in the growth regulation of NSCLC. In the current study nude mice carrying xenografts of the human lung NSCLC cell lines NCI-H322 or NCI-H441 were used as animal models. Nicotine administration and gamma aminobutyric acid (GABA) treatment lasted for 30 days. Catecholamines, cortisol, GABA, and cAMP were analyzed in blood and tumor tissues by immunoassays. Expression of nicotinic receptors and effector proteins in the xenografts was assessed by Western blotting. Our data indicate that nicotine stimulated the growth of NSCLC xenografts via modulation of nAChR upregulation and activation of cAMP signaling. The nicotine-treated group showed an enhanced level of stress neurotransmitters and second messenger cAMP in serum, blood cellular fraction, and xenograft tissues. Activation of critical proteins in the oncogenic pathway, including CREB, ERK, Akt, and Src, and upregulation of α-4 and α-7 subunits of nAChR provided mechanistic insight for the observed stimulatory effect of nicotine. Interestingly, GABA, being an antagonist to cAMP signaling, showed a promising intervention by reversing the stimulatory effect of nicotine on cancer growth and all signaling pathways. GABA has potential to lower the risk of NSCLC among smokers and could be used to enhance the clinical outcome of standard cancer intervention strategies.
Export Options
About this article
Cite this article as:
A.N. Al-Wadei H., H. Al-Wadei M., F. Ullah M. and M. Schuller H., Gamma-Amino Butyric Acid Inhibits the Nicotine-Imposed Stimulatory Challenge in Xenograft Models of Non-Small Cell Lung Carcinoma, Current Cancer Drug Targets 2012; 12 (2) . https://dx.doi.org/10.2174/156800912799095171
DOI https://dx.doi.org/10.2174/156800912799095171 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Role of IRF1 and IRF2 Transcription Factors in Leukaemogenesis
Current Gene Therapy Investigating the Molecular Basis of Drug Action and Response: Chemocentric Genomics and Proteomics
Current Drug Targets Evolution of Ipsilateral Head and Neck Radiotherapy
Current Cancer Therapy Reviews Molecular Docking, 3D-QSAR, Fingerprint-Based 2D-QSAR, Analysis of Pyrimidine, and Analogs of ALK (Anaplastic Lymphoma Kinase) Inhibitors as an Anticancer Agent
Letters in Drug Design & Discovery State of the Art of the Therapeutic Perspective of Sorafenib Against Hematological Malignancies
Current Medicinal Chemistry Destabilizing Aneuploidy by Targeting Cell Cycle and Mitotic Checkpoint Proteins in Cancer Cells
Current Drug Targets Summary of Information on the Effects of Ionizing and Non-ionizing Radiation on Cytochrome P450 and Other Drug Metabolizing Enzymes and Transporters
Current Drug Metabolism Dose and Sequence Dependent Synergism from the Combination of Oxaliplatin with Emetine and Patulin Against Colorectal Cancer
Anti-Cancer Agents in Medicinal Chemistry Improving Cancer Chemotherapy with Modulators of ABC Drug Transporters
Current Drug Targets Coumarins as Antioxidants
Current Medicinal Chemistry Cancer Control by Phytochemicals
Current Pharmaceutical Design 99mTechnetium- or Cy7-Labeled Fab(Tocilizumab) as Potential Multiple Myeloma Imaging Agents
Anti-Cancer Agents in Medicinal Chemistry Radiosyntheses using Fluorine-18: The Art and Science of Late Stage Fluorination
Current Topics in Medicinal Chemistry Silymarin in the Prevention and Treatment of Liver Diseases and Primary Liver Cancer
Current Pharmaceutical Biotechnology Molecular Imaging Kits for Hexosamine Biosynthetic Pathway in Oncology
Current Medicinal Chemistry Liver Stem Cells and Possible Clinical Applications
Current Stem Cell Research & Therapy Anti-Cancer Natural Product Library from Traditional Chinese Medicine
Combinatorial Chemistry & High Throughput Screening Estrogen Regulation of MicroRNA Expression
Current Genomics Editorial [Special Board Members Issue]
Current Drug Metabolism Interferon-Beta Therapy Monitoring in Multiple Sclerosis Patients
Endocrine, Metabolic & Immune Disorders - Drug Targets