Abstract
Cladribine, i.e.2-deoxy-Chloroadenosine is currently in use as chemotherapeutic agent in chronic lymphoid malignancies and pediatric acute myelogenous leukemia whereas the structurally related counterpart, 2-Chloroadenosine, has been less studied. Nevertheless, 2-Chloroadenosine has been shown to be capable of inducing apoptosis in several cell lines by acting either via adenosine receptors or via uptake that is followed by metabolic transformations leading to nucleotide analogues, i.e. antimetabolites effective in the treatment of a variety of malignancies. Triphosphate nucleoside analogues show specificity for cell in S-phase, inhibit DNA synthesis and kill the cells by mechanisms still largely unknown. 2-Chloroadenosine, at low micromolar concentration, acts as a metabolic precursor of an Sphase specific nucleoside analogue in human prostate cancer PC3 cells and inhibits DNA synthesis thereby leading to accumulation of cells in the S-phase. However, although responsible for the acquisition of resistance, the adenosine derivative is capable of sensitising the cells to the action of other antineoplastic agents and the ability of nucleoside analogues to trigger cell cycle arrest can be exploited to maximize cytotoxicity in combination with cell cycle checkpoint disregulators. 2-Chloroadenosine, in combination with Docetaxel, known to improve the survival of hormone-refractory prostate cancer patients, further decreases in vitro PC3 cell proliferation and invasiveness. Moreover, 2-Chloroadenosine is capable of modulating PAR-1 and IL-23 gene expression suggesting a modulation of cancer metastasis and immune system activity. The present review summarizes research performed in our laboratory to propose a novel role for 2-Chloroadenosine as an anticancer agent.
Keywords: Adenosine analogues, prostate cancer, cytotoxic effect, cytostatic effect, sensitization
Anti-Cancer Agents in Medicinal Chemistry
Title: 2-Chloroadenosine and Human Prostate Cancer Cells
Volume: 8 Issue: 7
Author(s): I. Bellezza, A. Tucci and A. Minelli
Affiliation:
Keywords: Adenosine analogues, prostate cancer, cytotoxic effect, cytostatic effect, sensitization
Abstract: Cladribine, i.e.2-deoxy-Chloroadenosine is currently in use as chemotherapeutic agent in chronic lymphoid malignancies and pediatric acute myelogenous leukemia whereas the structurally related counterpart, 2-Chloroadenosine, has been less studied. Nevertheless, 2-Chloroadenosine has been shown to be capable of inducing apoptosis in several cell lines by acting either via adenosine receptors or via uptake that is followed by metabolic transformations leading to nucleotide analogues, i.e. antimetabolites effective in the treatment of a variety of malignancies. Triphosphate nucleoside analogues show specificity for cell in S-phase, inhibit DNA synthesis and kill the cells by mechanisms still largely unknown. 2-Chloroadenosine, at low micromolar concentration, acts as a metabolic precursor of an Sphase specific nucleoside analogue in human prostate cancer PC3 cells and inhibits DNA synthesis thereby leading to accumulation of cells in the S-phase. However, although responsible for the acquisition of resistance, the adenosine derivative is capable of sensitising the cells to the action of other antineoplastic agents and the ability of nucleoside analogues to trigger cell cycle arrest can be exploited to maximize cytotoxicity in combination with cell cycle checkpoint disregulators. 2-Chloroadenosine, in combination with Docetaxel, known to improve the survival of hormone-refractory prostate cancer patients, further decreases in vitro PC3 cell proliferation and invasiveness. Moreover, 2-Chloroadenosine is capable of modulating PAR-1 and IL-23 gene expression suggesting a modulation of cancer metastasis and immune system activity. The present review summarizes research performed in our laboratory to propose a novel role for 2-Chloroadenosine as an anticancer agent.
Export Options
About this article
Cite this article as:
Bellezza I., Tucci A. and Minelli A., 2-Chloroadenosine and Human Prostate Cancer Cells, Anti-Cancer Agents in Medicinal Chemistry 2008; 8 (7) . https://dx.doi.org/10.2174/187152008785914725
DOI https://dx.doi.org/10.2174/187152008785914725 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
-
Nanotoxicity: The Toxicity Research Progress of Metal and Metal- Containing Nanoparticles
Mini-Reviews in Medicinal Chemistry Texaphyrins: Tumor Localizing Redox Active Expanded Porphyrins
Anti-Cancer Agents in Medicinal Chemistry Oxidized Polysaccharides as Green and Sustainable Biomaterials
Current Organic Chemistry Elevated O-GlcNAcylation Promotes Malignant Phenotypes of Hypopharyngeal Squamous Cell Carcinoma by Stabilizing Nrf2 through Regulation of the PI3K/Akt Pathway
Anti-Cancer Agents in Medicinal Chemistry Development of Peptide and Protein Based Radiopharmaceuticals
Current Pharmaceutical Design Vitamin D Supplementation and Cancer: Review of Randomized Controlled Trials
Anti-Cancer Agents in Medicinal Chemistry Evaluation of Pharmacological Treatment Strategies in Traumatic Brain Injury
Current Pharmaceutical Design Thiazoles and Thiazolidinones as Antioxidants
Current Medicinal Chemistry Immune Disturbances in Chronic Pain: Cause, Consequence or Both?
Current Immunology Reviews (Discontinued) The Role of Endothelin System in Cardiovascular Disease and the Potential Therapeutic Perspectives of its Inhibition
Current Topics in Medicinal Chemistry Intrinsic Disorder in Male Sex Determination: Disorderedness of Proteins from the Sry Transcriptional Network
Current Protein & Peptide Science Current Developments in the Analysis of Proteomic Data: Artificial Neural Network Data Mining Techniques for the Identification of Proteomic Biomarkers Related to Breast Cancer
Current Proteomics Novel Inhibitory Activity for Serine Protease Inhibitor Kazal Type-3 (Spink3) on Human Recombinant Kallikreins
Protein & Peptide Letters β -Glucans and their Applications in Cancer Therapy: Focus on human studies
Anti-Cancer Agents in Medicinal Chemistry Epigenetic Targeting of Platinum Resistant Testicular Cancer
Current Cancer Drug Targets Pharmacokinetic Profiles of Anticancer Herbal Medicines in Humans and the Clinical Implications
Current Medicinal Chemistry Synergistic Approaches to Clinical Oncology Biomarker Discovery
Current Topics in Medicinal Chemistry Chemically Modified Nano Crystalline Diamond Layer as Material Enhanced Laser Desorption Ionisation (MELDI) Surface in Protein Profiling
Current Nanoscience Inhibition of Autophagy by Targeting ATG4B: Promises and Challenges of An Emerging Anti-cancer Strategy
Clinical Cancer Drugs New Dehydroepiandrosterone-triazole Derivatives Identified as Inhibitors of 17β-Hydroxysteroid Dehydrogenase Enzyme in the Prostate
Current Enzyme Inhibition