Abstract
Protein kinase C (PKC) family members are multifunctional kinases that have been implicated in many cell biological and physiological tasks including acid, pepsinogen, and mucous production. Through the use of small-molecule PKC modulators, PKC has been found to be involved in gene expression, the control of cytoskeleton, membrane and secretagogue-dependent signal transduction for secretion of acid. Gastric carcinoma and adenocarcinoma cells often show dysregulated PKC-dependent cell signal transduction compared to normal gastric cells. Moreover, PKC was the first known target of tumor promoting phorbol esters. These findings support PKC as a potential chemotherapy target in gastric cancer. Various approaches have been launched in directly targeting PKC for chemotherapy of gastric cancer. The macrocyclic lactone bryostatin-1 is a promising agent that acts as a modulator of PKC activity, and enhances the effect of chemotherapeutic agents such as paclitaxel. This article provides an overview of the findings to date regarding the physiological role of PKC in the gastric cell system by various pharmacological approaches and examines PKC as a target in gastric (adeno-)carcinoma chemotherapy.
Keywords: bis(indolyl)maleimide, bryostatin, chemotherapy, gastric acid secretion, gastric cancer, indolocarbazole, phorbol ester, protein kinase C
Current Medicinal Chemistry
Title: Targeting Protein Kinase C (PKC) in Physiology and Cancer of the Gastric Cell System
Volume: 15 Issue: 12
Author(s): Michael Fahrmann
Affiliation:
Keywords: bis(indolyl)maleimide, bryostatin, chemotherapy, gastric acid secretion, gastric cancer, indolocarbazole, phorbol ester, protein kinase C
Abstract: Protein kinase C (PKC) family members are multifunctional kinases that have been implicated in many cell biological and physiological tasks including acid, pepsinogen, and mucous production. Through the use of small-molecule PKC modulators, PKC has been found to be involved in gene expression, the control of cytoskeleton, membrane and secretagogue-dependent signal transduction for secretion of acid. Gastric carcinoma and adenocarcinoma cells often show dysregulated PKC-dependent cell signal transduction compared to normal gastric cells. Moreover, PKC was the first known target of tumor promoting phorbol esters. These findings support PKC as a potential chemotherapy target in gastric cancer. Various approaches have been launched in directly targeting PKC for chemotherapy of gastric cancer. The macrocyclic lactone bryostatin-1 is a promising agent that acts as a modulator of PKC activity, and enhances the effect of chemotherapeutic agents such as paclitaxel. This article provides an overview of the findings to date regarding the physiological role of PKC in the gastric cell system by various pharmacological approaches and examines PKC as a target in gastric (adeno-)carcinoma chemotherapy.
Export Options
About this article
Cite this article as:
Fahrmann Michael, Targeting Protein Kinase C (PKC) in Physiology and Cancer of the Gastric Cell System, Current Medicinal Chemistry 2008; 15 (12) . https://dx.doi.org/10.2174/092986708784310413
DOI https://dx.doi.org/10.2174/092986708784310413 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Peptide and Non-peptide Antagonists Targeting Endothelin Receptors in Physiology and Pathology
Current Pharmaceutical Design Mitochondria and Familial Predisposition to Breast Cancer
Current Genomics Recent Progress in Medicinal Investigations on Trichosanthin and other Ribosome Inactivating Proteins from the Plant Genus Trichosanthes
Current Medicinal Chemistry Novel Lipid and Polymeric Materials as Delivery Systems for Nucleic Acid Based Drugs
Current Drug Metabolism Targeting CD4 to Disrupt Signaling Through Membrane Rafts: Towards a Raft-Based Therapeutics
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) 1,3,4-Thiadiazole Based Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Evolutionary Significance of Iodine
Current Chemical Biology Immunity to Bacterial Infections
Current Immunology Reviews (Discontinued) New Insights into the Regulation of Liver Inflammation and Oxidative Stress
Mini-Reviews in Medicinal Chemistry Study of Intercellular Adhesion Molecule-1 (ICAM-1) in Bone Homeostasis
Current Drug Targets Aquaporin Water Channels in Central Nervous System
Current Neurovascular Research miR-221/222 Confers Radioresistance in Glioblastoma Cells Through Activating Akt Independent of PTEN Status
Current Molecular Medicine The Urokinase Plasminogen Activator System: Role in Malignancy
Current Pharmaceutical Design Challenges and Perspectives in the Discovery of Dengue Virus Entry Inhibitors
Current Medicinal Chemistry A Brief Review of the Essential Role of Nanovehicles for Improving the Therapeutic Efficacy of Pharmacological Agents Against Tumours
Current Drug Delivery Effects of Dietary Non-Fiber Carbohydrates on Composition and Function of Gut Microbiome in Monogastrics: A Review
Protein & Peptide Letters Structure-Activity Relationship Study of a Series of N-Substituted Piperazinyl-Fluoroquinolones as Anti-Helicobacter pylori Agents
Medicinal Chemistry Ferrous Ion Chelating Modification and Treatment of Iron-Deficiency Anemia of Exopolysaccharide from Lachnum sp.
Current Chemical Biology Xanthomicrol: A Comprehensive Review of Its Chemistry, Distribution, Biosynthesis and Pharmacological Activity
Mini-Reviews in Medicinal Chemistry Inhibiting HSP90 to Treat Cancer: A Strategy in Evolution
Current Molecular Medicine