Abstract
The anti-tumor therapeutic ellipticine and its derivatives act as potent anticancer agents via a combined mechanism involving cell cycle arrest and induction of apoptosis. Cell death induced by ellipticine has been shown to engage a p53-dependent pathway, cell cycle arrest, interaction with several kinases and induction of the mitochondrial pathway of apoptotic cell death. Cell cycle arrest was shown to result from DNA damage caused by a variety of tumor chemotherapeutic agents; this is also the case for ellipticines. The prevalent DNA-mediated mechanisms of anti-tumor, mutagenic and cytotoxic activities of ellipticine are (i) intercalation into DNA, (ii) inhibition of DNA topoisomerase II activity, and (iii) covalent binding to DNA in vitro and in vivo after enzymatic activation by cytochrome P450 and/or peroxidase enzymes The mechanism leading to apoptosis by ellipticine is thought to also be associated with DNA damage, by inhibition of topoisomerase II and the covalent modification of DNA. In addition, the formation of ellipticine-DNA adducts ultimately can mutate cancer cells or initiate cell death. The aim of this review is to summarize our knowledge on the molecular mechanisms with the aim to explain the effectiveness of ellipticines as DNA-targeted chemotherapeutics in cancer cells.
Keywords: Anticancer drugs, DNA-damaging drugs, ellipticines, mechanisms of ellipticine anticancer action, apoptosis.
Current Medicinal Chemistry
Title:Ellipticines as DNA-Targeted Chemotherapeutics
Volume: 21 Issue: 5
Author(s): Marie Stiborova and Eva Frei
Affiliation:
Keywords: Anticancer drugs, DNA-damaging drugs, ellipticines, mechanisms of ellipticine anticancer action, apoptosis.
Abstract: The anti-tumor therapeutic ellipticine and its derivatives act as potent anticancer agents via a combined mechanism involving cell cycle arrest and induction of apoptosis. Cell death induced by ellipticine has been shown to engage a p53-dependent pathway, cell cycle arrest, interaction with several kinases and induction of the mitochondrial pathway of apoptotic cell death. Cell cycle arrest was shown to result from DNA damage caused by a variety of tumor chemotherapeutic agents; this is also the case for ellipticines. The prevalent DNA-mediated mechanisms of anti-tumor, mutagenic and cytotoxic activities of ellipticine are (i) intercalation into DNA, (ii) inhibition of DNA topoisomerase II activity, and (iii) covalent binding to DNA in vitro and in vivo after enzymatic activation by cytochrome P450 and/or peroxidase enzymes The mechanism leading to apoptosis by ellipticine is thought to also be associated with DNA damage, by inhibition of topoisomerase II and the covalent modification of DNA. In addition, the formation of ellipticine-DNA adducts ultimately can mutate cancer cells or initiate cell death. The aim of this review is to summarize our knowledge on the molecular mechanisms with the aim to explain the effectiveness of ellipticines as DNA-targeted chemotherapeutics in cancer cells.
Export Options
About this article
Cite this article as:
Stiborova Marie and Frei Eva, Ellipticines as DNA-Targeted Chemotherapeutics, Current Medicinal Chemistry 2014; 21 (5) . https://dx.doi.org/10.2174/09298673113206660272
DOI https://dx.doi.org/10.2174/09298673113206660272 |
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
![](/images/wayfinder.jpg)
- 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
-
Curcumin Inhibits Vasculogenic Mimicry <i>via</i> Regulating ETS-1 in Renal
Cell Carcinoma
Current Cancer Drug Targets Acetylation Control of Cancer Cell Metabolism
Current Pharmaceutical Design Application of Click Chemistry for PET
Current Organic Chemistry SUMOylation Modulates CFTR Biogenesis: Is the Pathway Druggable?
Current Drug Targets The Role of Apoptotic Dysfunction in the Pathogenesis of Endometriosis
Current Women`s Health Reviews Update to: The Aryl Hydrocarbon Receptor in Anticancer Drug Discovery: Friend or Foe?
Medicinal Chemistry Reviews - Online (Discontinued) Somatostatin, Somatostatin Analogs and Somatostatin Receptor Dynamics in the Biology of Cancer Progression
Current Molecular Medicine Neurokinin-1 Receptor (NK-1R) Antagonists: Potential Targets in the Treatment of Glioblastoma Multiforme
Current Medicinal Chemistry Editorial [Hot Topic: Beyond Gynaecological Cancers: Psychological Challenges (Guest Editor: Vania Goncalves)]
Current Women`s Health Reviews CDK Inhibitors: From the Bench to Clinical Trials
Current Drug Targets The Potential Therapeutic Role of the HMGB1-TLR Pathway in Epilepsy
Current Drug Targets Intra-uterine Growth Retardation as a Risk Factor of Postnatal Metabolic Disorders
Current Pharmaceutical Biotechnology The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) Family of Proteins: Transcriptional Modifiers with Multi-Functional Protein Interfaces
Current Molecular Medicine Bioinformatics Analysis Predicts hsa_circ_0026337/miR-197-3p as a Potential Oncogenic ceRNA Network for Non-Small Cell Lung Cancers
Anti-Cancer Agents in Medicinal Chemistry Progress in Research on Tumor Metastasis Inhibitors
Current Medicinal Chemistry Perioperative Management of Female Hormone Medications
Current Clinical Pharmacology Impact of Sex Hormone Metabolism on the Vascular Effects of Menopausal Hormone Therapy in Cardiovascular Disease
Current Drug Metabolism Epigenetics: Relations to Disease and Laboratory Findings
Current Medicinal Chemistry MtDNA As a Cancer Marker: A Finally Closed Chapter?
Current Genomics Role of Progesterone in Human Astrocytomas Growth
Current Topics in Medicinal Chemistry