Abstract
Inorganic arsenic is an environmental human carcinogen, and has been shown to act as a co-carcinogen with solar ultraviolet (UV) radiation in mouse skin tumor induction even at low concentrations. However, the precise mechanism of its co-carcinogenic action is largely unknown. Apoptosis plays an essential role as a protective mechanism against neoplastic development in the organism by eliminating genetically damaged cells. Thus, suppression of apoptosis is thought to contribute to carcinogenesis. It is known that cyclooxygenase-2 (COX-2) can promote carcinogenesis by inhibiting cell apoptosis under stress conditions; and our current studies investigated the potential contribution of COX-2 to the inhibitory effect of arsenite in UV-induced cell apoptosis in mouse epidermal Cl41 cells. We found that treatment of cells with low concentration (5 μM) arsenite attenuated cellular apoptosis upon UVB radiation accompanied with a coinductive effect on COX-2 expression and nuclear factor-κB (NFκB) transactivation. Our results also showed that the COX-2 induction by arsenite and UVB depended on an NFκB pathway because COX-2 co-induction could be attenuated in either p65-deficient or p50-deficient cells. Moreover, UVB-induced cell apoptosis could be dramatically reduced by the introduction of exogenous COX-2 expression, whereas the inhibitory effect of arsenite on UVB-induced cell apoptosis could be impaired in COX-2 knockdown C141 cells. Our results indicated that COX-2 mediated the anti-apoptotic effect of arsenite in UVB radiation through an NFκB-dependent pathway. Given the importance of apoptosis evasion during carcinogenesis, we anticipated that COX-2 induction might be at least partially responsible for the co-carcinogenic effect of arsenite on UVB-induced skin carcinogenesis.
Keywords: Apoptosis, arsenite, COX-2, NF-κB, UVB, activator protein-1, B-cell lymphoma-2, B-cell lymphoma-extra large, bronchial epithelial cell line, Dulbecco's Modified Eagle’s Medium, fetal bovine serum, heme oxygenase 1, mouse embryonic fibroblasts, minimal essential medium
Current Cancer Drug Targets
Title:Cyclooxygenase-2 (COX-2) Mediates Arsenite Inhibition of UVB-Induced Cellular Apoptosis in Mouse Epidermal Cl41 Cells
Volume: 12 Issue: 6
Author(s): Z. Zuo, W. Ouyang, J. Li, M. Costa and C. Huang
Affiliation:
Keywords: Apoptosis, arsenite, COX-2, NF-κB, UVB, activator protein-1, B-cell lymphoma-2, B-cell lymphoma-extra large, bronchial epithelial cell line, Dulbecco's Modified Eagle’s Medium, fetal bovine serum, heme oxygenase 1, mouse embryonic fibroblasts, minimal essential medium
Abstract: Inorganic arsenic is an environmental human carcinogen, and has been shown to act as a co-carcinogen with solar ultraviolet (UV) radiation in mouse skin tumor induction even at low concentrations. However, the precise mechanism of its co-carcinogenic action is largely unknown. Apoptosis plays an essential role as a protective mechanism against neoplastic development in the organism by eliminating genetically damaged cells. Thus, suppression of apoptosis is thought to contribute to carcinogenesis. It is known that cyclooxygenase-2 (COX-2) can promote carcinogenesis by inhibiting cell apoptosis under stress conditions; and our current studies investigated the potential contribution of COX-2 to the inhibitory effect of arsenite in UV-induced cell apoptosis in mouse epidermal Cl41 cells. We found that treatment of cells with low concentration (5 μM) arsenite attenuated cellular apoptosis upon UVB radiation accompanied with a coinductive effect on COX-2 expression and nuclear factor-κB (NFκB) transactivation. Our results also showed that the COX-2 induction by arsenite and UVB depended on an NFκB pathway because COX-2 co-induction could be attenuated in either p65-deficient or p50-deficient cells. Moreover, UVB-induced cell apoptosis could be dramatically reduced by the introduction of exogenous COX-2 expression, whereas the inhibitory effect of arsenite on UVB-induced cell apoptosis could be impaired in COX-2 knockdown C141 cells. Our results indicated that COX-2 mediated the anti-apoptotic effect of arsenite in UVB radiation through an NFκB-dependent pathway. Given the importance of apoptosis evasion during carcinogenesis, we anticipated that COX-2 induction might be at least partially responsible for the co-carcinogenic effect of arsenite on UVB-induced skin carcinogenesis.
Export Options
About this article
Cite this article as:
Zuo Z., Ouyang W., Li J., Costa M. and Huang C., Cyclooxygenase-2 (COX-2) Mediates Arsenite Inhibition of UVB-Induced Cellular Apoptosis in Mouse Epidermal Cl41 Cells, Current Cancer Drug Targets 2012; 12 (6) . https://dx.doi.org/10.2174/156800912801784802
DOI https://dx.doi.org/10.2174/156800912801784802 |
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 Urokinase Receptor in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Modulation of Matrix Metalloproteinases by Plant-derived Products
Current Cancer Drug Targets A Survey on the Applications of Implantable Micropump Systems in Drug Delivery
Current Drug Delivery The Complex Actions of Statins in Brain and their Relevance for Alzheimer`s Disease Treatment: An Analytical Review
Current Alzheimer Research Impact of Renin-Angiotensin System in Hepatocellular Carcinoma
Current Cancer Drug Targets Influence of Genetic Factors on the Development of Breast Cancer in the Older Woman
Current Aging Science Radioprotective Gene Therapy
Current Gene Therapy TGF-Beta Type I Receptor (Alk5) Kinase Inhibitors in Oncology
Current Pharmaceutical Biotechnology Genome-wide Differential-based Analysis of the Relationship between DNA Methylation and Gene Expression in Cancer
Current Bioinformatics A Review of Diabetes Mellitus and Exposure to the Environmental Toxicant Cadmium with an Emphasis on Likely Mechanisms of Action
Current Diabetes Reviews Hypoxia and Inflammation in Prostate Cancer Progression. Cross-talk with Androgen and Estrogen Receptors and Cancer Stem Cells
Endocrine, Metabolic & Immune Disorders - Drug Targets Potential of Gene Therapy for the Treatment of Pituitary Tumors
Current Gene Therapy Serotonin and Cancer: What Is the Link?
Current Molecular Medicine The p53-Estrogen Receptor Loop in Cancer
Current Molecular Medicine HIF Prolyl-4-hydroxylase Interacting Proteins: Consequences for Drug Targeting
Current Pharmaceutical Design An Update on the Systemic Therapy of Malignant Salivary Gland Cancers: Role of Chemotherapy and Molecular Targeted Agents
Current Medicinal Chemistry - Anti-Cancer Agents TRPM6 and TRPM7: A Mul-TRP-PLIK-Cation of Channel Functions
Current Pharmaceutical Biotechnology RAGE: A Multi-Ligand Receptor Unveiling Novel Insights in Health and Disease
Current Medicinal Chemistry The Role of Androgen Under Normal and Pathological Conditions in Sebaceous Glands: The Possibility of Target Therapy
Current Molecular Pharmacology A Comprehensive Outline of Trastuzumab Resistance Biomarkers in HER2 Overexpressing Breast Cancer
Current Cancer Drug Targets