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
-
Phytoestrogens and Mitochondrial Biogenesis in Breast Cancer. Influence of Estrogen Receptors Ratio
Current Pharmaceutical Design Dendritic Cells and their Receptors in Antitumor Immune Response
Current Molecular Medicine Druggable Orthosteric and Allosteric Hot Spots to Target Protein-protein Interactions
Current Pharmaceutical Design Chemical Modifications of Two Polysaccharides as Drug Carriers
Current Organic Synthesis Targeted Therapies in Gynecologic Cancers
Current Cancer Drug Targets Anti-Cancer Targeting Telomerase Inhibitors: β-Rubromycin and Oleic Acid
Mini-Reviews in Medicinal Chemistry Namitecan: a Hydrophilic Camptothecin with a Promising Preclinical Profile
Current Medicinal Chemistry Nucleic Acid-based Technologies in Therapy of Malignant Gliomas
Current Pharmaceutical Biotechnology Role of Osmolytes in Regulating Immune System
Current Pharmaceutical Design Leptomeningeal Metastasis: Challenges in Diagnosis and Treatment
Current Cancer Therapy Reviews P-gp Inhibition-Based Strategies for Modulating Pharmacokinetics of Anticancer Drugs: An Update
Current Drug Metabolism Prophylactic Admission of an In Vitro Reconstructed Complexes of Human Recombinant Heat Shock Proteins and Melanoma Antigenic Peptides Activates Anti-Melanoma Responses in Mice
Current Molecular Medicine Down Regulated Expression of Claudin-1 and Claudin-5 and Up Regulation of β-Catenin: Association with Human Glioma Progression
CNS & Neurological Disorders - Drug Targets P38 MAPK Contributes to Resistance and Invasiveness of HER2- Overexpressing Breast Cancer
Current Medicinal Chemistry Current Application of Quantum Dots (QD) in Cancer Therapy: A Review
Mini-Reviews in Medicinal Chemistry Nitric Oxide and the Regulation of Apoptosis in Tumour Cells
Current Pharmaceutical Design Effect of Drugs in Cells and Tissues by NMR Spectroscopy
Current Topics in Medicinal Chemistry Recent Developments of Magnetic Nanoparticles for Theranostics of Brain Tumor
Current Drug Metabolism Insulin Resistance, Oxidative Stress and Cardiovascular Complications: Role of Sirtuins
Current Pharmaceutical Design Snake Venom L-Amino Acid Oxidases: Some Consideration About their Functional Characterization
Protein & Peptide Letters