Abstract
Lung cancer (LC) remains the leading cause of cancer mortality worldwide, and non-small cell LC (NSCLC) represents 80% of all LC. Oxidative stress and inflammation, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-κB, and mitogen activated protein kinases (MAPK) participate in LC pathophysiology. Currently available treatment for LC is limited and in vivo models are lacking. We hypothesized that antioxidants and NF- κB, MAPK, and proteasome inhibitors may exert an antitumoral response through attenuation of several key biological mechanisms that promote tumorigenesis and cancer cell growth. Body and tumor weights, oxidative stress, antioxidants, inflammation, NF-κB p65 expression, fibulins, apoptosis, autophagy, tumor and stroma histology were evaluated in the subcutaneous tumor of LC (LP07 adenocarcinoma) BALB/c mice, with and without concomitant treatment with NF-κB (sulfasalazine), MEK (U0126), and proteasome (bortezomib) inhibitors, and N-acetyl cysteine (NAC). Compared to LC control mice, in subcutanous tumors, the four pharmacological agents reduced oxidative stress markers and tumor proliferation (ki-67). Inflammation and NF-κB p65 expression were attenuated by NF-κB and MAPK inhibitors, and the latter also enhanced apoptotic markers. Catalase was induced by the three inhibitors, while bortezomib also promoted superoxide dismutase expression. NF-κB and MEK inhibitors significantly reduced tumor burden through several biological mechanisms that favored tumor degradation and attenuated tumor proliferation. These two pharmacological agents may enhance the anti-tumor activity of selectively targeted therapeutic strategies for LC. Proteasomal inhibition using bortezomib rather promotes tumor degradation, while treatment with antioxidants cannot be recommended. This experimental model supports the use of adjuvant drugs for the improvement of LC treatment.
Keywords: Lung adenocarcinoma, therapeutic strategies, stromal structure, tumor proliferation, apoptosis, autophagy, redox imbalance, inflammation.
Current Pharmaceutical Design
Title:Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology
Volume: 22 Issue: 34
Author(s): Mercè Mateu-Jimenez, Clara Fermoselle, Federico Rojo, Javier Mateu, Raúl Peña, Alejandro J. Urtreger, Miriam J. Diament, Elisa D. Bal de Kier Joffé, Lara Pijuan, Antonio García de Herreros and Esther Barreiro
Affiliation:
Keywords: Lung adenocarcinoma, therapeutic strategies, stromal structure, tumor proliferation, apoptosis, autophagy, redox imbalance, inflammation.
Abstract: Lung cancer (LC) remains the leading cause of cancer mortality worldwide, and non-small cell LC (NSCLC) represents 80% of all LC. Oxidative stress and inflammation, autophagy, ubiquitin-proteasome system, nuclear factor (NF)-κB, and mitogen activated protein kinases (MAPK) participate in LC pathophysiology. Currently available treatment for LC is limited and in vivo models are lacking. We hypothesized that antioxidants and NF- κB, MAPK, and proteasome inhibitors may exert an antitumoral response through attenuation of several key biological mechanisms that promote tumorigenesis and cancer cell growth. Body and tumor weights, oxidative stress, antioxidants, inflammation, NF-κB p65 expression, fibulins, apoptosis, autophagy, tumor and stroma histology were evaluated in the subcutaneous tumor of LC (LP07 adenocarcinoma) BALB/c mice, with and without concomitant treatment with NF-κB (sulfasalazine), MEK (U0126), and proteasome (bortezomib) inhibitors, and N-acetyl cysteine (NAC). Compared to LC control mice, in subcutanous tumors, the four pharmacological agents reduced oxidative stress markers and tumor proliferation (ki-67). Inflammation and NF-κB p65 expression were attenuated by NF-κB and MAPK inhibitors, and the latter also enhanced apoptotic markers. Catalase was induced by the three inhibitors, while bortezomib also promoted superoxide dismutase expression. NF-κB and MEK inhibitors significantly reduced tumor burden through several biological mechanisms that favored tumor degradation and attenuated tumor proliferation. These two pharmacological agents may enhance the anti-tumor activity of selectively targeted therapeutic strategies for LC. Proteasomal inhibition using bortezomib rather promotes tumor degradation, while treatment with antioxidants cannot be recommended. This experimental model supports the use of adjuvant drugs for the improvement of LC treatment.
Export Options
About this article
Cite this article as:
Mateu-Jimenez Mercè, Fermoselle Clara, Rojo Federico, Mateu Javier, Peña Raúl, Urtreger J. Alejandro, Diament J. Miriam, Joffé D. Bal de Kier Elisa, Pijuan Lara, Herreros García de Antonio and Barreiro Esther, Pharmacological Approaches in an Experimental Model of Non-Small Cell Lung Cancer: Effects on Tumor Biology, Current Pharmaceutical Design 2016; 22 (34) . https://dx.doi.org/10.2174/1381612822666160623065523
DOI https://dx.doi.org/10.2174/1381612822666160623065523 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Panobinostat: The Small Molecule Metalloenzyme Inhibitor with Marvelous Anticancer Activity
Current Topics in Medicinal Chemistry Nontoxic-dose of Deguelin Induce NPMc+ AML Cell Differentiation by Selectively Targeting Mt NPM1/SIRT1 Instead of HDAC1/3
Current Cancer Drug Targets Multiple-Target Drugs: Inhibitors of Heat Shock Protein 90 and of Histone Deacetylase
Current Drug Targets Recent Developments of Platinum-based Anticancer Drugs- Detection and Analysis in Biological Samples
Current Organic Chemistry Small Peptides as Modulators of Serine Proteases
Current Medicinal Chemistry Scalarane Sesterterpenoids
Current Bioactive Compounds Suramin: Clinical Uses and Structure-Activity Relationships
Mini-Reviews in Medicinal Chemistry Differential Modulation of Autophagy Contributes to the Protective Effects of Resveratrol and Co-Enzyme Q10 in Photoaged Mice
Current Molecular Pharmacology The Frequency of Thrombotic Events Among Adults Given Antifibrinolytic Drugs for Spontaneous Bleeding: Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials
Current Drug Safety Toxicities of Immunosuppressive Treatment of Autoimmune Neurologic Diseases
Current Neuropharmacology Best Practices and Emerging Trends for Market Access to Personalised Medicine in the US and EU: Learnings for Global Developed and Emerging Markets
Current Pharmacogenomics and Personalized Medicine uPAR as Anti-Cancer Target: Evaluation of Biomarker Potential, Histological Localization, and Antibody-Based Therapy
Current Drug Targets Epigenetic Multiple Modulators
Current Topics in Medicinal Chemistry Novel Implications for Lysophospholipids, Lysophosphatidic Acid and Sphingosine 1-Phosphate, as Drug Targets in Cancer
Anti-Cancer Agents in Medicinal Chemistry Current Options in the Treatment of Mast Cell Mediator-Related Symptoms in Mastocytosis
Inflammation & Allergy - Drug Targets (Discontinued) Combretastatin A-4 Analogs as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Thalidomide as an Antiangiogenic Drug in the Treatment of Multiple Myeloma
Letters in Drug Design & Discovery Increase in the Non-HIV-Related Deaths Among Aids Cases in the HAART Era
Current HIV Research Computational Modeling of Dielectrophoretic Microfluidic Channel for Simultaneous Separation of Red Blood Cells and Platelets
Current Signal Transduction Therapy Nanoparticles in Gastric Cancer Management
Current Pharmaceutical Design