Abstract
Longitudinal bone growth is a complex and tightly regulated process. A precise balance between proliferation, differentiation and cell death in growth plate chondrocytes is a key to normal bone growth in children. Indeed, decrease in proliferation/differentiation and increase in undesired cell death in growth plate cartilage are directly associated with impaired bone growth. Proteasome inhibitors are currently undergoing phase I and II clinical trials to evaluate their efficacy in the treatment of various childhood cancers. Effects of proteasome inhibitors on bone growth in children have not yet been reported. However, recent preclinical observations suggest that proteasome inhibitors may selectively target essential cell populations in growth plate cartilage, causing significant growth failure; an effect associated with increased apoptosis and decreased proliferation of chondrocytes. The observed effects on apoptosis and proliferation in growth plate chondrocytes appear to be mediated by several proteins including p53, apoptosis inducing factor (AIF), caspases, NF-κB and β-catenine. These observations could have important implications for the use of proteasome inhibitors in the treatment of childhood diseases.
Keywords: Growth Plate, chondrocytes, bone, Apoptosis, proteasome inhibitors, Autophagy, cell death, apoptosis inducing factor (AIF), bortezomib, anti-cancer agents
Current Pediatric Reviews
Title: Double-Edged Sword of Novel Anti-Cancer Treatment: Proteasome Inhibition in the Growth Plate Causes Impairment of Longitudinal Bone Growth
Volume: 7 Issue: 4
Author(s): Farasat Zaman, Bengt Fadeel and Lars Savendahl
Affiliation:
Keywords: Growth Plate, chondrocytes, bone, Apoptosis, proteasome inhibitors, Autophagy, cell death, apoptosis inducing factor (AIF), bortezomib, anti-cancer agents
Abstract: Longitudinal bone growth is a complex and tightly regulated process. A precise balance between proliferation, differentiation and cell death in growth plate chondrocytes is a key to normal bone growth in children. Indeed, decrease in proliferation/differentiation and increase in undesired cell death in growth plate cartilage are directly associated with impaired bone growth. Proteasome inhibitors are currently undergoing phase I and II clinical trials to evaluate their efficacy in the treatment of various childhood cancers. Effects of proteasome inhibitors on bone growth in children have not yet been reported. However, recent preclinical observations suggest that proteasome inhibitors may selectively target essential cell populations in growth plate cartilage, causing significant growth failure; an effect associated with increased apoptosis and decreased proliferation of chondrocytes. The observed effects on apoptosis and proliferation in growth plate chondrocytes appear to be mediated by several proteins including p53, apoptosis inducing factor (AIF), caspases, NF-κB and β-catenine. These observations could have important implications for the use of proteasome inhibitors in the treatment of childhood diseases.
Export Options
About this article
Cite this article as:
Zaman Farasat, Fadeel Bengt and Savendahl Lars, Double-Edged Sword of Novel Anti-Cancer Treatment: Proteasome Inhibition in the Growth Plate Causes Impairment of Longitudinal Bone Growth, Current Pediatric Reviews 2011; 7 (4) . https://dx.doi.org/10.2174/157339611796892319
DOI https://dx.doi.org/10.2174/157339611796892319 |
Print ISSN 1573-3963 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6336 |
![](/images/wayfinder.jpg)
- 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
-
Intracellular ROS Generation Mediates Maleimide-induced Cytotoxicity in Leukemia Cells
Anti-Cancer Agents in Medicinal Chemistry Lipoprotein (a) and Cardiovascular Risk: The Show Must go on
Current Medicinal Chemistry Recent Advances for Cell / Gene Therapy in Rheumatoid Arthritis
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Critical Illness in Obstetric Patients: Venous Thromboembolism in Pregnancy
Current Women`s Health Reviews Clinical Application and Synthesis Methods of Deuterated Drugs
Current Medicinal Chemistry When Does Food Refusal Require Professional Intervention?
Current Nutrition & Food Science AAV-Mediated Gene Transfer for Treatment of Hemophilia
Current Gene Therapy Roles of Renal Proximal Tubule Transport in the Pathogenesis of Hypertension
Current Hypertension Reviews Plasticity of Neuroendocrine-Immune Interactions During Ontogeny: Role of Perinatal Programming in Pathogenesis of Inflammation and Stress- Related Diseases in Adults
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Single Nucleotide Polymorphisms as the Efficient Prognostic Markers in Breast Cancer
Current Cancer Drug Targets Pro-apoptotic Activity of BH3-only Proteins and BH3 Mimetics: from Theory to Potential Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Immune Modulation by Regulatory T Cells in Helicobacter pylori-Associated Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Patent Selections:
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Omalizumab for Asthma: Indications, Off-Label Uses and Future Directions
Recent Patents on Inflammation & Allergy Drug Discovery Gastric Teratoma in an Adult Female Patient: A Case Report
Current Medical Imaging Adjuvant and Neoadjuvant Chemotherapy for Soft Tissue Sarcomas
Current Medicinal Chemistry High Dose Immunoglobulin (IVIG) May Reduce the Incidence of Langerhans Cell Histiocytosis (LCH)-Associated Central Nervous System Involvement
CNS & Neurological Disorders - Drug Targets Unique Insights into the Actions of CNS Agents: Lessons from Studies of Chlorpyrifos and Other Common Pesticides
Central Nervous System Agents in Medicinal Chemistry Anti-NMDA Receptor Encephalitis in Psychiatry
Current Psychiatry Reviews Neuro-Transmitters in the Central Nervous System & their Implication in Learning and Memory Processes
Current Medicinal Chemistry