Abstract
Phenylbutyrate (PBA) is an aromatic short-chain fatty acid which is a chemical derivative of butyric acid naturally produced by colonic bacteria fermentation. At the intestinal level butyrate exerts a multitude of activities including amelioration of mucosal inflammation, regulation of transepithelial fluid transport, improvement in oxidative status and colon cancer prevention. Moreover, increasing number of studies report the beneficial role of butyric acid in prevention or inhibition of other types of malignancies, leading to cancer cell growth arrest and apoptosis. Similarly, phenylbutyrate displays potentially favorable effects on many pathologies including cancer, genetic metabolic syndromes, neuropathies, diabetes, hemoglobinopathies, and urea cycle disorders. The mechanisms by which PBA exerts these effects are different. Some of them are connected with the regulation of gene expression, playing the role of a histone deacetylase inhibitor, while others contribute to the ability of rescuing conformational abnormalities of proteins, serving as chemical chaperone, and some are dedicated to its metabolic characteristic enabling excretion of toxic ammonia, thus acting as ammonia scavenger. Phenylbutyrate may exert variable effects depending on the cell type, thus the term “butyrate paradox” has been proposed. These data indicate a broad spectrum of beneficial effects evoked by PBA with a high potential in therapy. In this review, we focus on cellular and systemic effects of PBA treatment with special attention to the three main branches of its molecular activity: ammonia scavenging, chaperoning and histone deacetylase inhibiting, and describe its particular role in various human diseases.
Keywords: Ammonia scavenger, butyric acid, chemical chaperone, ER stress, histone deacetylase inhibitor, phenylbutyrate.
Current Pharmaceutical Design
Title:Phenylbutyric Acid: Simple Structure - Multiple Effects
Volume: 21 Issue: 16
Author(s): Magdalena Kusaczuk, Marek Bartoszewicz and Marzanna Cechowska-Pasko
Affiliation:
Keywords: Ammonia scavenger, butyric acid, chemical chaperone, ER stress, histone deacetylase inhibitor, phenylbutyrate.
Abstract: Phenylbutyrate (PBA) is an aromatic short-chain fatty acid which is a chemical derivative of butyric acid naturally produced by colonic bacteria fermentation. At the intestinal level butyrate exerts a multitude of activities including amelioration of mucosal inflammation, regulation of transepithelial fluid transport, improvement in oxidative status and colon cancer prevention. Moreover, increasing number of studies report the beneficial role of butyric acid in prevention or inhibition of other types of malignancies, leading to cancer cell growth arrest and apoptosis. Similarly, phenylbutyrate displays potentially favorable effects on many pathologies including cancer, genetic metabolic syndromes, neuropathies, diabetes, hemoglobinopathies, and urea cycle disorders. The mechanisms by which PBA exerts these effects are different. Some of them are connected with the regulation of gene expression, playing the role of a histone deacetylase inhibitor, while others contribute to the ability of rescuing conformational abnormalities of proteins, serving as chemical chaperone, and some are dedicated to its metabolic characteristic enabling excretion of toxic ammonia, thus acting as ammonia scavenger. Phenylbutyrate may exert variable effects depending on the cell type, thus the term “butyrate paradox” has been proposed. These data indicate a broad spectrum of beneficial effects evoked by PBA with a high potential in therapy. In this review, we focus on cellular and systemic effects of PBA treatment with special attention to the three main branches of its molecular activity: ammonia scavenging, chaperoning and histone deacetylase inhibiting, and describe its particular role in various human diseases.
Export Options
About this article
Cite this article as:
Kusaczuk Magdalena, Bartoszewicz Marek and Cechowska-Pasko Marzanna, Phenylbutyric Acid: Simple Structure - Multiple Effects, Current Pharmaceutical Design 2015; 21 (16) . https://dx.doi.org/10.2174/1381612821666150105160059
DOI https://dx.doi.org/10.2174/1381612821666150105160059 |
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
-
Cytokines Play a Key Role in Communication between Mesenchymal Stem Cells and Brain Cancer Cells
Protein & Peptide Letters Synthesis and Biological Evaluation of 2´-Hydroxy-4´,6´-Diprenyloxychal-Cone Derivatives as Potent CDC25B and PTP1B Inhibitors
Letters in Drug Design & Discovery Radiogenetic Therapy: Strategies to Overcome Tumor Resistance
Current Pharmaceutical Design Current Development of Metal Complexes with Diamine Ligands as Potential Anticancer Agents
Current Medicinal Chemistry Adenovirus Vectors Composed of Subgroup B Adenoviruses
Current Gene Therapy Channel-Like Functions of the 18-kDa Translocator Protein (TSPO): Regulation of Apoptosis and Steroidogenesis as Part of the Host-Defense Response
Current Pharmaceutical Design Meet Our Associate Editor
Current Molecular Medicine Antisense Oligonucleotides in the Treatment of Cerebral Gliomas. Review of Concerning Patents
Recent Patents on CNS Drug Discovery (Discontinued) Base Excision Repair: Contribution to Tumorigenesis and Target in Anticancer Treatment Paradigms
Current Medicinal Chemistry Ligand-Targeted Liposomes for Cancer Treatment
Current Drug Delivery Interconnection of Estrogen/Testosterone Metabolism and Mevalonate Pathway in Breast and Prostate Cancers
Current Molecular Pharmacology Natural Compounds as Inhibitors of SARS-CoV-2 Main Protease (3CLpro): A Molecular Docking and Simulation Approach to Combat COVID-19
Current Pharmaceutical Design Seeing Genes at Work in the Living Brain with Non-Invasive Molecular Imaging
Current Gene Therapy Targeting the JAK/STAT Signaling Pathway for Breast Cancer
Current Medicinal Chemistry Tracking Stem Cells for Cellular Therapy in Stroke
Current Pharmaceutical Design Targeting the Mevalonate Pathway for Improved Anticancer Therapy
Current Cancer Drug Targets Curcumin: A Promising Agent Targeting Cancer Stem Cells
Anti-Cancer Agents in Medicinal Chemistry Revisiting Non-Cancer Drugs for Cancer Therapy
Current Topics in Medicinal Chemistry MicroRNA-34 Family, Mechanisms of Action in Cancer: A Review
Current Cancer Drug Targets Berberine Exerts Anti-cancer Activity by Modulating Adenosine Monophosphate- Activated Protein Kinase (AMPK) and the Phosphatidylinositol 3-Kinase/ Protein Kinase B (PI3K/AKT) Signaling Pathways
Current Pharmaceutical Design