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
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
-
Autoantibody Profiles as Biomarkers for Response to Therapy and Early Detection of Cancer
Current Cancer Therapy Reviews Integrative Analysis of miRNA-mediated Competing Endogenous RNA Network Reveals the lncRNAs-mRNAs Interaction in Glioblastoma Stem Cell Differentiation
Current Bioinformatics Rational Combination of Targeted Therapies As A Strategy to Overcome The Mechanisms of Resistance to Inhibitors of EGFR Signaling
Current Pharmaceutical Design Multi-Targeted Agents in Cancer Cell Chemosensitization: What We Learnt from Curcumin Thus Far
Recent Patents on Anti-Cancer Drug Discovery Analytical Techniques for Determining Pharmaceutical Residues in Drinking Water – State of Art and Future Prospects
Current Analytical Chemistry Druggability of Mortalin for Cancer and Neuro-Degenerative Disorders
Current Pharmaceutical Design Aging and DNA Methylation
Current Chemical Biology Epi-Drugs and Epi-miRs: Moving Beyond Current Cancer Therapies
Current Cancer Drug Targets Intraoperative Targeted Optical Imaging: A Guide towards Tumor-Free Margins in Cancer Surgery
Current Pharmaceutical Biotechnology Role of Polyamines in Breast Cancer Growth, Development and Progression
Current Cancer Therapy Reviews Anti-EGFR Binding Nanobody Delivery System to Improve the Diagnosis and Treatment of Solid Tumours
Recent Patents on Anti-Cancer Drug Discovery Thrombophilia and Female Sex Hormones
Current Women`s Health Reviews Chemotherapy and Delivery in the Treatment of Primary Brain Tumors
Current Clinical Pharmacology Prognosis, Significance and Positive Correlation of Rab1A and p-S6K/Gli1 Expression in Gastric Cancer
Anti-Cancer Agents in Medicinal Chemistry HOXB7 and Hsa-miR-222 as the Potential Therapeutic Candidates for Metastatic Colorectal Cancer
Recent Patents on Anti-Cancer Drug Discovery High Throughput Study for Molecular Mechanism of Metformin Pre-Diabetic Protection <i>via</i> Microarray Approach
Endocrine, Metabolic & Immune Disorders - Drug Targets New Approaches to Target Cancer Stem Cells: Current Scenario
Mini-Reviews in Medicinal Chemistry Combined Treatment with Octreotide, Galanin and Serotonin in Gastrointestinal Malignancies
Letters in Drug Design & Discovery Applications of Barton-McCombie Reaction in Total Syntheses
Current Organic Synthesis MicroRNA Therapeutics: The Emerging Anticancer Strategies
Recent Patents on Anti-Cancer Drug Discovery