Abstract
We succeeded in purifying a major glycolipids fraction (i.e., Fraction-II) in the class of monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG) and sulfoquinovosyl diacylglycerol (SQDG) from spinach using hydrophobic column chromatography. Fraction-II inhibited the activities of replicative DNA polymerases (pols) such as α, δ and η, and mitochondrial pol g with IC50 values of 43 - 79 μg/ml, but had no influence on the activity of repair-related pols β and lλ. MGDG, DGDG, SQDG were purified from Fraction-II of spinach using silica gel column chromatography, and SQDG was the strongest inhibitor of mammalian pols in the three glycolipids. Therefore, SQDG and its related compounds were chemically synthesized, and the sulfate group and fatty acid moiety of the compound were suggested to be important for pol inhibition. These glycolipids showed no effect even on the activities of plant pols, prokaryotic pols and other DNA metabolic enzymes such as T4 polynucleotide kinase, T7 RNA polymerase and deoxyribonuclease I. Fraction-II also inhibited the proliferation of human cervix carcinoma (HeLa) cells with LD50 values of 57 μg/ml, and could halt the cell cycle at the G1-phase, and subsequently induced severe apoptosis. In an in vivo anti-tumor assay on nude mice bearing solid tumors of HeLa cells, Fraction-II was shown to be a promising suppressor of solid tumors. Histopathological examination revealed that tumor necrosis with hemorrhage was significantly enhanced with Fraction-II in vivo. The spinach Fraction-II containing SQDG might be a potent anti-tumor compound, and may be a healthy food substance with antitumor activity.
Keywords: Glycolipids, monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG), sulfoquinovosyl diacylglycerol (SQDG), DNA polymerase, inhibitor, anti-tumor activity, spinach
Current Medicinal Chemistry
Title: Inhibitory Effect on Replicative DNA Polymerases, Human Cancer Cell Proliferation, and In Vivo Anti-Tumor Activity by Glycolipids from Spinach
Volume: 14 Issue: 9
Author(s): Naoki Maeda, Takahiko Hada, Hiromi Yoshida and Yoshiyuki Mizushina
Affiliation:
Keywords: Glycolipids, monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG), sulfoquinovosyl diacylglycerol (SQDG), DNA polymerase, inhibitor, anti-tumor activity, spinach
Abstract: We succeeded in purifying a major glycolipids fraction (i.e., Fraction-II) in the class of monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG) and sulfoquinovosyl diacylglycerol (SQDG) from spinach using hydrophobic column chromatography. Fraction-II inhibited the activities of replicative DNA polymerases (pols) such as α, δ and η, and mitochondrial pol g with IC50 values of 43 - 79 μg/ml, but had no influence on the activity of repair-related pols β and lλ. MGDG, DGDG, SQDG were purified from Fraction-II of spinach using silica gel column chromatography, and SQDG was the strongest inhibitor of mammalian pols in the three glycolipids. Therefore, SQDG and its related compounds were chemically synthesized, and the sulfate group and fatty acid moiety of the compound were suggested to be important for pol inhibition. These glycolipids showed no effect even on the activities of plant pols, prokaryotic pols and other DNA metabolic enzymes such as T4 polynucleotide kinase, T7 RNA polymerase and deoxyribonuclease I. Fraction-II also inhibited the proliferation of human cervix carcinoma (HeLa) cells with LD50 values of 57 μg/ml, and could halt the cell cycle at the G1-phase, and subsequently induced severe apoptosis. In an in vivo anti-tumor assay on nude mice bearing solid tumors of HeLa cells, Fraction-II was shown to be a promising suppressor of solid tumors. Histopathological examination revealed that tumor necrosis with hemorrhage was significantly enhanced with Fraction-II in vivo. The spinach Fraction-II containing SQDG might be a potent anti-tumor compound, and may be a healthy food substance with antitumor activity.
Export Options
About this article
Cite this article as:
Maeda Naoki, Hada Takahiko, Yoshida Hiromi and Mizushina Yoshiyuki, Inhibitory Effect on Replicative DNA Polymerases, Human Cancer Cell Proliferation, and In Vivo Anti-Tumor Activity by Glycolipids from Spinach, Current Medicinal Chemistry 2007; 14 (9) . https://dx.doi.org/10.2174/092986707780362952
DOI https://dx.doi.org/10.2174/092986707780362952 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
Insights into the Role of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Health and Disease
Current Chemical Biology Targeting Matrix Metalloproteinases in Inflammatory Conditions
Current Drug Targets Tumor-Associated Macrophages as Potential Targets for Anti-Cancer Activity of Marine Invertebrate-Derived Compounds
Current Pharmaceutical Design Transforming Growth Factor Beta in Pancreatic Cancer
Current Pharmaceutical Biotechnology Recent Trends in Oral Drug Delivery: A Review
Recent Patents on Drug Delivery & Formulation Naturally Occurring Hydroxytyrosol: Synthesis and Anticancer Potential
Current Medicinal Chemistry Peptides as Tight Junction Modulators
Current Pharmaceutical Design Profiling of Autophagy-Associated microRNAs in the Osteosarcoma Cell Line of U2OS
Anti-Cancer Agents in Medicinal Chemistry Meet Our Editorial Board Member
Current Drug Delivery Ultrasound-Triggered Immunotherapy for Cancer Treatment: An Update
Current Protein & Peptide Science Opportunities and Challenges in Nano-structure Mediated Drug Delivery: Where Do We Stand?
Current Nanomedicine Choline Kinase Alpha Depletion Selectively Kills Tumoral Cells
Current Cancer Drug Targets Patent Selections:
Recent Patents on Drug Delivery & Formulation Role of TGF- β in the Tumor Stroma
Current Cancer Drug Targets The Mediterranean Diet and Gastrointestinal Cancers Risk
Recent Patents on Food, Nutrition & Agriculture Novel Serine Protease Dipeptidyl Peptidase IV Inhibitor: Alogliptin
Mini-Reviews in Medicinal Chemistry Isomers of 4-[<sup>18</sup>F]fluoro-proline: Radiosynthesis, Biological Evaluation and Results in Humans Using PET
Current Radiopharmaceuticals Remodelling of the Ca2+ Toolkit in Tumor Endothelium as a Crucial Responsible for the Resistance to Anticancer Therapies
Current Signal Transduction Therapy Urtica dioica Extract Inhibits Cell Proliferation and Induces Apoptosis in HepG2 and HTC116 as Gastrointestinal Cancer Cell Lines
Anti-Cancer Agents in Medicinal Chemistry Inhibition of Cellular Proliferation by Drug Targeting of Cyclin-Dependent Kinases
Current Pharmaceutical Biotechnology