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
-
Repurposing Pharmaceuticals as Neuroprotective Agents for Cerebral Malaria
Current Clinical Pharmacology Reprograming Carcinoma Associated Fibroblasts by microRNAs
Current Molecular Medicine Histone Deacetylase Inhibitors: Potent Anti-Leukemic Agents
Current Medicinal Chemistry Targeting Focal Adhesion Kinase in Neuroblastoma
Anti-Cancer Agents in Medicinal Chemistry Targeting Angiogenesis in Head and Neck Cancer
Current Cancer Drug Targets Environmental Pollution and Asthma
Current Respiratory Medicine Reviews Emerging Roles of P2X Receptors in Cancer
Current Medicinal Chemistry Editorial [Hot Topic: Stem Cells and Tissue Regeneration (Executive Guest Editor: Roberta Di Pietro)]
Current Pharmaceutical Design Nitrosative Stress as a Mediator of Apoptosis: Implications for Cancer Therapy
Current Pharmaceutical Design Radiolabelled Peptides and Monoclonal Antibodies for Therapy Decision Making in Inflammatory Diseases
Current Pharmaceutical Design Genetics and Genomics Interventions for Promoting Millets as Functional Foods
Current Genomics Pathobiology and Therapeutic Implications of Tumor Acidosis
Current Medicinal Chemistry 5q- syndrome
Current Pharmaceutical Design Treatment of Acute Hypercalcemia
Medicinal Chemistry SCYL1-BP1 Affects Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells via Cyclin F and RRM2
Anti-Cancer Agents in Medicinal Chemistry Biomarkers of Asthma: Recent Patents from 2009-2011
Recent Patents on Biomarkers Pyridine Based Antitumour Compounds Acting at the Colchicine Site
Current Medicinal Chemistry Thalidomide: An Overview of its Pharmacological Mechanisms of Action
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Isolation of Secreted microRNAs (miRNAs) from Cell-conditioned Media
MicroRNA Pleiotropic Effect of Mahanine and Girinimbine Analogs: Anticancer Mechanism and its Therapeutic Versatility
Anti-Cancer Agents in Medicinal Chemistry