Abstract
Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor gamma (PPARγ) ligand, is known to have anti-tumor activity by inducing tumor cell apoptosis. However, it is unknown whether it can be used to prevent smoking carcinogen-induced lung tumor development. We induced mouse lung tumors using smoking carcinogen 4- methylnitrosamino-l-3-pyridyl-butanone (NNK). PGZ was given at two early stages before the tumor formation. The role and the functional mechanism of PGZ were investigated in the development of mouse pulmonary tumors. The tumor development was monitored and PPARγ activity and endogenous PPARγ ligands 15(S)-HETE, 13(S)-HODE were determined. The application of PGZ before alveolar hyperplasia formation (Group NPa) and at the early phase of alveolar hyperplasia formation (Group NPb) significantly prevented the lung tumor development especially in Group NPb mice (all p<0.05). PGZ not only prevented the NNK-mediated reduction of endogenous ligands 15(S)-HETE and 13(S)-HODE, but also increased 13(S)-HODE level in Group NPb mice. PPARγ transcriptional activity was increased in NNKstimulated lung tissues when PGZ was given. The in vivo results were confirmed in the human lung cancer cells, which showed that PGZ induced lung cancer cell apoptosis through up-regulating nuclear PPARγ expression, inducing PPARγ transcriptional activity and increasing the levels of PPARγ ligands in NNK-treated cells. The early application of PGZ is able to prevent NNK-induced lung tumor development through maintaining the level of endogenous PPARγ ligands 15(S)-HETE and 13(S)-HODE and activation of PPARγ.
Keywords: Lung tumor development, pioglitazone, PPARγ, 15(S)-HETE, 13(S)-HODE, smoking carcinogen NNK, thiazolidinediones, troglitazone, PPARγ coactivator-1 alpha, 13-S-hydroxyoctadecadienoic acid, peroxisome proliferator-activated receptor gamma, PPARγ coactivator-1 alpha
Current Cancer Drug Targets
Title:Pioglitazone Prevents Smoking Carcinogen-Induced Lung Tumor Development in Mice
Volume: 12 Issue: 6
Author(s): M. -Y. Li, A. W.Y. Kong, H. Yuan, L. T. Ma, M. K.Y. Hsin, I. Y.P. Wan, M. J. Underwood and G. G. Chen
Affiliation:
Keywords: Lung tumor development, pioglitazone, PPARγ, 15(S)-HETE, 13(S)-HODE, smoking carcinogen NNK, thiazolidinediones, troglitazone, PPARγ coactivator-1 alpha, 13-S-hydroxyoctadecadienoic acid, peroxisome proliferator-activated receptor gamma, PPARγ coactivator-1 alpha
Abstract: Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor gamma (PPARγ) ligand, is known to have anti-tumor activity by inducing tumor cell apoptosis. However, it is unknown whether it can be used to prevent smoking carcinogen-induced lung tumor development. We induced mouse lung tumors using smoking carcinogen 4- methylnitrosamino-l-3-pyridyl-butanone (NNK). PGZ was given at two early stages before the tumor formation. The role and the functional mechanism of PGZ were investigated in the development of mouse pulmonary tumors. The tumor development was monitored and PPARγ activity and endogenous PPARγ ligands 15(S)-HETE, 13(S)-HODE were determined. The application of PGZ before alveolar hyperplasia formation (Group NPa) and at the early phase of alveolar hyperplasia formation (Group NPb) significantly prevented the lung tumor development especially in Group NPb mice (all p<0.05). PGZ not only prevented the NNK-mediated reduction of endogenous ligands 15(S)-HETE and 13(S)-HODE, but also increased 13(S)-HODE level in Group NPb mice. PPARγ transcriptional activity was increased in NNKstimulated lung tissues when PGZ was given. The in vivo results were confirmed in the human lung cancer cells, which showed that PGZ induced lung cancer cell apoptosis through up-regulating nuclear PPARγ expression, inducing PPARγ transcriptional activity and increasing the levels of PPARγ ligands in NNK-treated cells. The early application of PGZ is able to prevent NNK-induced lung tumor development through maintaining the level of endogenous PPARγ ligands 15(S)-HETE and 13(S)-HODE and activation of PPARγ.
Export Options
About this article
Cite this article as:
-Y. Li M., W.Y. Kong A., Yuan H., T. Ma L., K.Y. Hsin M., Y.P. Wan I., J. Underwood M. and G. Chen G., Pioglitazone Prevents Smoking Carcinogen-Induced Lung Tumor Development in Mice, Current Cancer Drug Targets 2012; 12 (6) . https://dx.doi.org/10.2174/156800912801784848
DOI https://dx.doi.org/10.2174/156800912801784848 |
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
-
Immunity to Tuberculosis and Novel Therapeutic Strategies
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) Preface
Current Medical Imaging Indole-3-ethylsulfamoylphenylacrylamides with Potent Anti-proliferative and Anti-angiogenic Activities
Anti-Cancer Agents in Medicinal Chemistry Retinoids as Critical Modulators of Immune Functions: New Therapeutic Perspectives for Old Compounds
Endocrine, Metabolic & Immune Disorders - Drug Targets Bisphosphonate Anticancer Activity in Prostate Cancer and Other Genitourinary Cancers
Anti-Cancer Agents in Medicinal Chemistry Tissue-Based Approaches to Study Pharmacodynamic Endpoints in Early Phase Oncology Clinical Trials
Current Drug Targets Development of A Novel System Based on Green Magnetic / Graphene Oxide / Chitosan /Allium Sativum / Quercus / Nanocomposite for Targeted Release of Doxorubicin Anti-Cancer Drug
Anti-Cancer Agents in Medicinal Chemistry Vitamin D Deficiency: Universal Risk Factor for Multifactorial Diseases?
Current Drug Targets The Medicinal Chemistry Implications of the Anticancer Effects of Aspirin and Other NSAIDs
Mini-Reviews in Medicinal Chemistry Targeted Therapy for Advanced Urothelial Cancer of the Bladder: Where Do We Stand?
Anti-Cancer Agents in Medicinal Chemistry ROCK Inhibitors as Emerging Therapeutic Candidates for Sarcomas
Current Cancer Drug Targets Advanced Assessment of the Endogenous Hormone Level as a Potential Biomarker of the Urogenital Tract Cancer
Combinatorial Chemistry & High Throughput Screening MMPs in Ovarian Cancer as Therapeutic Targets
Anti-Cancer Agents in Medicinal Chemistry Paclitaxel Efficacy is Increased by Parthenolide via Nuclear Factor- KappaB Pathways in In Vitro and In Vivo Human Non–Small Cell Lung Cancer Models
Current Cancer Drug Targets Selenium Derivatives as Cancer Preventive Agents
Current Medicinal Chemistry - Anti-Cancer Agents The Changing Face of HIV/AIDS in Treated Patients
Current HIV Research Editorial (Thematic Issue: Antiangiogenic Agents in the Management of Solid Malignancies)
Current Angiogenesis (Discontinued) Adeno-Associated Virus-Mediated Gene Transfer in Hematopoietic Stem/Progenitor Cells as a Therapeutic Tool
Current Gene Therapy PROGRAMMED Cell Clearance: Molecular Mechanisms and Role in Autoimmune Disease, Chronic Inflammation, and Anti-Cancer Immune Responses
Current Immunology Reviews (Discontinued) Synthesis, Characterization, Antimicrobial and Antitumor Activities of Sucrose Octa(N-ethyl)carbamate
Medicinal Chemistry