Abstract
Protein kinase C (PKC) comprises a family of isozymes (α, βI, βII,γ δ, ε, θ, & eegr;, λ/ι [mouse/human], and ζ) which are involved in signal transduction from membrane receptors to the nucleus. Activation of PKC by phorbol esters promotes tumor formation, and from that it was concluded that inhibitors of PKC might prevent carcinogenesis or inhibit tumor proliferation. However, the situation is more complicated because the exact function of the different PKC isozymes is not known at present. They have been shown to be involved in synaptic transmissions, the activation of ion fluxes, secretion, cell cycle control, differentiation, proliferation, tumorigenesis, metastasis and apoptosis. Modulators such as bryostatin-1, phospholipid analogues, PKC-activating adriamycin derivatives, CGP41251, UCN-01, and antisense oligonucleotides directed against PKCα, have shown antitumor activity in cancer patients. PKC inhibitors are not specific to PKC, but also interact with other signaling molecules, which may contribute to the antitumor effects. Modulators of PKC have also been shown to influence non-MDR1-mediated and MDR1- mediated antitumor drug resistance. This review is focussed on the role of PKC isozymes in human cell proliferation, apoptosis and antitumor drug resistance, and on the use of PKC modulators as antitumor agents.
Keywords: CGP41251, isozymes, apoptosis, antitumor agents, PKC modulators
Current Cancer Drug Targets
Title: Protein Kinase C Isozymes as Potential Targets for Anticancer Therapy
Volume: 4 Issue: 2
Author(s): Johann Hofmann
Affiliation:
Keywords: CGP41251, isozymes, apoptosis, antitumor agents, PKC modulators
Abstract: Protein kinase C (PKC) comprises a family of isozymes (α, βI, βII,γ δ, ε, θ, & eegr;, λ/ι [mouse/human], and ζ) which are involved in signal transduction from membrane receptors to the nucleus. Activation of PKC by phorbol esters promotes tumor formation, and from that it was concluded that inhibitors of PKC might prevent carcinogenesis or inhibit tumor proliferation. However, the situation is more complicated because the exact function of the different PKC isozymes is not known at present. They have been shown to be involved in synaptic transmissions, the activation of ion fluxes, secretion, cell cycle control, differentiation, proliferation, tumorigenesis, metastasis and apoptosis. Modulators such as bryostatin-1, phospholipid analogues, PKC-activating adriamycin derivatives, CGP41251, UCN-01, and antisense oligonucleotides directed against PKCα, have shown antitumor activity in cancer patients. PKC inhibitors are not specific to PKC, but also interact with other signaling molecules, which may contribute to the antitumor effects. Modulators of PKC have also been shown to influence non-MDR1-mediated and MDR1- mediated antitumor drug resistance. This review is focussed on the role of PKC isozymes in human cell proliferation, apoptosis and antitumor drug resistance, and on the use of PKC modulators as antitumor agents.
Export Options
About this article
Cite this article as:
Hofmann Johann, Protein Kinase C Isozymes as Potential Targets for Anticancer Therapy, Current Cancer Drug Targets 2004; 4 (2) . https://dx.doi.org/10.2174/1568009043481579
DOI https://dx.doi.org/10.2174/1568009043481579 |
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
-
Convection Enhanced Delivery of Macromolecules for Brain Tumors
Current Drug Discovery Technologies Improving Safety of Gene Therapy
Current Drug Safety The Role of the RhoA/rho-kinase Pathway in Pulmonary Hypertension
Current Drug Discovery Technologies Natural and Engineered Cystine Knot Miniproteins for Diagnostic and Therapeutic Applications
Current Pharmaceutical Design Dendrimers As Vectors for Genetic Material Delivery to the Nervous System
Current Medicinal Chemistry Electrochemical Cell-based Biosensors for Biomedical Applications
Current Topics in Medicinal Chemistry Non-Invasive Cell Tracking in Cancer and Cancer Therapy
Current Topics in Medicinal Chemistry Pharmacogenetics of Non-small Cell Lung Cancer (NSCLC): Time to "Work it Out"?
Current Pharmaceutical Design Bleomycin Induced Sensitivity to TRAIL/Apo-2L-Mediated Apoptosis in Human Seminomatous Testicular Cancer Cells is Correlated with Upregulation of Death Receptors
Anti-Cancer Agents in Medicinal Chemistry Symmetry Plane Detection in Brain Image Analysis: A Survey
Current Medical Imaging Recent Advances in the Development of Catalytic Inhibitors of Human DNA Topoisomerase IIα As Novel Anticancer Agents
Current Medicinal Chemistry Matching Chelators to Radiometals for Positron Emission Tomography Imaging- Guided Targeted Drug Delivery
Current Drug Targets Polyphenols and Neuroprotection against Ischemia and Neurodegeneration
Mini-Reviews in Medicinal Chemistry ZIP4 is a Novel Diagnostic and Prognostic Marker in Human Pancreatic Cancer: A Systemic Comparison Between EUS-FNA and Surgical Specimens
Current Molecular Medicine Presence of Intratumoral Stem Cells in Breast Cancer Patients with or without BRCA Germline Mutations
Current Cancer Drug Targets Protein-Modified Magnetic Nanoparticles for Biomedical Applications
Current Organic Chemistry Editorial
Current Medical Imaging The Interplay between Indoleamine 2,3-Dioxygenase 1 (IDO1) and Cyclooxygenase (COX)-2 In Chronic Inflammation and Cancer
Current Medicinal Chemistry Recent Advances of Poly(ether-ether) and Poly(ether-ester) Block Copolymers in Biomedical Applications
Current Drug Metabolism “Micromanaging” Glioblastoma Multiforme: The Potential of MicroRNAs, Circular RNAs, and the Hippo Pathway as Novel Treatment Strategies
Current Neurovascular Research