Abstract
This paper describes the inhibitory activities of diacylglyceride phospholipids, such as phosphatidylcholine (lecithin), phosphatidylethanolamine (cephalin), phosphatidylserine, phosphatidylglycerol, bisphosphatidylglycerol (cardiolipin), phosphatidylinositol, and phosphatidic acid (phosphatidate) (compounds 1–7, respectively) against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compounds 3–7 were revealed to be potent inhibitors of animal pols: compound 4 was the strongest inhibitor, with IC50 values for different pols of 1.7 – 15 μM. Compounds 4–7 also inhibited the activity of human topo II: compound 7 was the strongest inhibitor, with an IC50 value of 20 μM. The glycerophospholipids had no effect on the activities of plant (cauliflower) pol α, prokaryotic pols, or other DNA metabolic enzymes, such as calf primase of pol α, T7 RNA polymerase, T4 polynucleotide kinase, and bovine deoxyribonuclease I. These results suggest that compounds 4–7 are selective inhibitors of animal pols and human topos. Compounds 4 and 7 also suppressed the growth of a human colon carcinoma cell line that lacked p53 (HCT116 p53-/-); their LD50 values were 63.6 and 51.1 μM, respectively, suggesting that cell growth inhibition by these compounds leads to the inhibition of pols and/or topos. From these findings, diacylglyceride phospholipids, which are present in various foods, might be effective nutrients for promoting human anti-cancer health promotion.
Keywords: Diacylglyceride phospholipids, Phosphatidylglycerol, Phosphatidic acid (Phosphatidate), Enzyme inhibitor, DNA polymerase, DNA topoisomerase, Cancer cell growth suppression
Medicinal Chemistry
Title: Inhibitory Effects of Diacylglyceride Phospholipids on DNA Polymerase and Topoisomerase Activities, and Human Cancer Cell Growth
Volume: 6 Issue: 3
Author(s): Chisato Ishimaru, Toshifumi Takeuchi, Fumio Sugawara, Hiromi Yoshida and Yoshiyuki Mizushina
Affiliation:
Keywords: Diacylglyceride phospholipids, Phosphatidylglycerol, Phosphatidic acid (Phosphatidate), Enzyme inhibitor, DNA polymerase, DNA topoisomerase, Cancer cell growth suppression
Abstract: This paper describes the inhibitory activities of diacylglyceride phospholipids, such as phosphatidylcholine (lecithin), phosphatidylethanolamine (cephalin), phosphatidylserine, phosphatidylglycerol, bisphosphatidylglycerol (cardiolipin), phosphatidylinositol, and phosphatidic acid (phosphatidate) (compounds 1–7, respectively) against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compounds 3–7 were revealed to be potent inhibitors of animal pols: compound 4 was the strongest inhibitor, with IC50 values for different pols of 1.7 – 15 μM. Compounds 4–7 also inhibited the activity of human topo II: compound 7 was the strongest inhibitor, with an IC50 value of 20 μM. The glycerophospholipids had no effect on the activities of plant (cauliflower) pol α, prokaryotic pols, or other DNA metabolic enzymes, such as calf primase of pol α, T7 RNA polymerase, T4 polynucleotide kinase, and bovine deoxyribonuclease I. These results suggest that compounds 4–7 are selective inhibitors of animal pols and human topos. Compounds 4 and 7 also suppressed the growth of a human colon carcinoma cell line that lacked p53 (HCT116 p53-/-); their LD50 values were 63.6 and 51.1 μM, respectively, suggesting that cell growth inhibition by these compounds leads to the inhibition of pols and/or topos. From these findings, diacylglyceride phospholipids, which are present in various foods, might be effective nutrients for promoting human anti-cancer health promotion.
Export Options
About this article
Cite this article as:
Ishimaru Chisato, Takeuchi Toshifumi, Sugawara Fumio, Yoshida Hiromi and Mizushina Yoshiyuki, Inhibitory Effects of Diacylglyceride Phospholipids on DNA Polymerase and Topoisomerase Activities, and Human Cancer Cell Growth, Medicinal Chemistry 2010; 6 (3) . https://dx.doi.org/10.2174/1573406411006030114
DOI https://dx.doi.org/10.2174/1573406411006030114 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
-
Cytogenetic and Molecular Abnormalities in Myelodysplastic Syndrome
Current Molecular Medicine Monoclonal Antibodies: A Target Therapy for Multiple Sclerosis
Inflammation & Allergy - Drug Targets (Discontinued) Analysis of Drug Transport Kinetics in Multidrug-resistant Cells: Implications for Drug Action
Current Medicinal Chemistry Targeting Transcription Factors for Cancer Therapy
Current Pharmaceutical Design The Breakthroughs in Cancer Immune Checkpoint Based Therapy: A Review of Development in Immune Checkpoint Study and its Application
Combinatorial Chemistry & High Throughput Screening Anti-Apoptotic Actions of Insulin-Like Growth Factors: Lessons from Development and Implications in Neoplastic Cell Transformation
Current Pharmaceutical Design Laboratory Diagnosis and Therapy of Invasive Fungal Infections
Current Drug Targets Genetic Variants in Genes Involved in Mechanisms of Chemoresistance to Anticancer Drugs
Current Cancer Drug Targets Arterial Ischemic Stroke in Neonates and Children: Review and Current Issues
Current Pediatric Reviews Design of Lipophilic Prodrugs to Improve Drug Delivery and Efficacy
Current Drug Targets PET Radiopharmaceuticals for Personalized Medicine
Current Drug Targets Immobilized Using Nanotechnology of Electron-Beam Synthesis Regulators of Progenitor Cells Functions: Remedies of New Generation for Regenerative Medicine
Recent Patents on Regenerative Medicine Electroporation Gene Therapy Preclinical and Clinical Trials for Melanoma
Current Gene Therapy Drug Delivery Systems for Chemotherapeutics through Selected Polysaccharidic Vehicles
Current Organic Chemistry Phytochemicals as Adjunctive with Conventional Anticancer Therapies
Current Pharmaceutical Design Contextualizing the Genes Altered in Bladder Neoplasms in Pediatric and Teen Patients Allows Identifying Two Main Classes of Biological Processes Involved and New Potential Therapeutic Targets
Current Genomics microRNA Biogenesis Pathway as a Therapeutic Target for Human Disease and Cancer
Current Pharmaceutical Design The Immunoproteasome: An Emerging Therapeutic Target
Current Topics in Medicinal Chemistry Mouse Models of Autoimmune Diseases: Immune Thrombocytopenia
Current Pharmaceutical Design Recent Patents on Molecular Cytogenetics
Recent Patents on DNA & Gene Sequences