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
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...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
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...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
- 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
-
Flexible Estrogen Receptor Modulators: Synthesis, Biochemistry and Molecular Modeling Studies for 3-Benzyl-4,6-diarylhex-3-ene and 3,4,6-Triarylhex-3-ene Derivatives
Medicinal Chemistry Therapeutic Potential of Perineural Invasion, Hypoxia and Desmoplasia in Pancreatic Cancer
Current Pharmaceutical Design Episensitization: Therapeutic Tumor Resensitization by Epigenetic Agents: A Review and Reassessment
Anti-Cancer Agents in Medicinal Chemistry Aging and Oral Health: Effects in Hard and Soft Tissues
Current Pharmaceutical Design Understanding the Design Principles of Living Systems at the Nanoscale
Current Nanoscience Three Decades of P-gp Inhibitors: Skimming Through Several Generations and Scaffolds
Current Medicinal Chemistry Necrosis Avidity of Organic Compounds: A Natural Phenomenon with Exploitable Theragnostic Potentials
Current Medicinal Chemistry Cancer Cell Reprogramming: Stem Cell Differentiation Stage Factors and An Agent Based Model to Optimize Cancer Treatment
Current Pharmaceutical Biotechnology Clinical Significance of Thiopurine S-Methyltransferase Gene Polymorphisms
Current Pharmacogenomics Development of Novel Therapeutic Strategies for Lung Cancer: Targeting the Cholinergic System
Current Medicinal Chemistry Recent Advances in Polymeric Nanosystems for Treating Cutaneous Melanoma and Its Metastasis
Current Pharmaceutical Design Targeted Liposomal Drug Delivery in Cancer
Current Pharmaceutical Design Therapeutical Approaches of Vasoactive Intestinal Peptide as a Pleiotropic Immunomodulator
Current Pharmaceutical Design Chemical Properties and Biological Activities of Cyclopentenediones: A Review
Mini-Reviews in Medicinal Chemistry Human Embryonic and Induced Pluripotent Stem Cell Based Toxicity Testing Models: Future Applications in New Drug Discovery
Current Medicinal Chemistry Histone Deacetylase Inhibitors: Recent Insights from Basic to Clinical Knowledge & Patenting of Anti-Cancer Actions
Recent Patents on Anti-Cancer Drug Discovery Altered Glycosylation of Proteins in Cancer: What Is the Potential for New Anti-Tumour Strategies
Anti-Cancer Agents in Medicinal Chemistry Diagnostic Accuracy of F18-fluorodeoxyglucose Positron Emission Tomography- computed Tomography for the Detection of Non-small Cell Lung Cancer Recurrence: A Systematic Review and Meta-analysis
Current Medical Imaging Opposite Effects of Two-Derived Antioxidants from Physalis pubescens L. on Hepatocellular Carcinoma Cell Line Malhavu
Current Pharmaceutical Biotechnology Redox Status in Periodontal and Systemic Inflammatory Conditions Including Associated Neoplasias: Antioxidants as Adjunctive Therapy?
Infectious Disorders - Drug Targets