Abstract
Angiogenesis plays an important role in tumor metastasis and progression, and thus inhibiting angiogenesis is a promising strategy for treatment of cancer. However, tumor-associated angiogenesis is influenced by various angiogenic factors in the tumor microenvironment. Thymidine phosphorylase (TP, EC 2. 4. 2. 4), an enzyme involved in the reversible conversion of thymidine to thymine, is an important mediator of angiogenesis, tumorigenicity, metastasis and invasion. The angiogenic effect of TP requires the enzymatic activity of TP. TP activity is expressed at higher levels in a wide variety of solid tumors than in adjacent non-neoplastic tissue. The tumor microenvironment (hypoxia, acidosis) regulates the expression of TP, and TP expression in tumor tissue shows significant correlation with microvessel density and poor prognosis. 2-Deoxy-D-ribose (D-dRib), one of the degradation products of thymidine generated by TP activity, promotes angiogenesis and the chemotactic activity of endothelial cells and also confers resistance to hypoxia-induced apoptosis in some cancer cell lines. These findings suggest that D-dRib is a downstream mediator of TP function. 2-Deoxy-L-ribose, a stereoisomer of D-dRib, can inhibit D-dRibs anti-apoptotic effects and suppress metastasis and invasion of TP-expressing tumors in mice. Although the mechanism of action of D-dRib is still unknown, the physiological activities of D-dRib have recently been reported by several groups. We review the role of D-dRib in tumor progression and discuss inhibition of D-dRib as a promising approach for chemotherapy of various tumors.
Keywords: 2-Deoxy-D-ribose, 2-Deoxy-L-ribose, thymidine phosphorylase, angiogenesis, hypoxia-induced apoptosis, metastasis, invasion, tumor microenvironment
Anti-Cancer Agents in Medicinal Chemistry
Title: 2-Deoxy-D-Ribose, a Downstream Mediator of Thymidine Phosphorylase, Regulates Tumor Angiogenesis and Progression
Volume: 9 Issue: 2
Author(s): Yuichi Nakajima, Radha Madhyastha and Masugi Maruyama
Affiliation:
Keywords: 2-Deoxy-D-ribose, 2-Deoxy-L-ribose, thymidine phosphorylase, angiogenesis, hypoxia-induced apoptosis, metastasis, invasion, tumor microenvironment
Abstract: Angiogenesis plays an important role in tumor metastasis and progression, and thus inhibiting angiogenesis is a promising strategy for treatment of cancer. However, tumor-associated angiogenesis is influenced by various angiogenic factors in the tumor microenvironment. Thymidine phosphorylase (TP, EC 2. 4. 2. 4), an enzyme involved in the reversible conversion of thymidine to thymine, is an important mediator of angiogenesis, tumorigenicity, metastasis and invasion. The angiogenic effect of TP requires the enzymatic activity of TP. TP activity is expressed at higher levels in a wide variety of solid tumors than in adjacent non-neoplastic tissue. The tumor microenvironment (hypoxia, acidosis) regulates the expression of TP, and TP expression in tumor tissue shows significant correlation with microvessel density and poor prognosis. 2-Deoxy-D-ribose (D-dRib), one of the degradation products of thymidine generated by TP activity, promotes angiogenesis and the chemotactic activity of endothelial cells and also confers resistance to hypoxia-induced apoptosis in some cancer cell lines. These findings suggest that D-dRib is a downstream mediator of TP function. 2-Deoxy-L-ribose, a stereoisomer of D-dRib, can inhibit D-dRibs anti-apoptotic effects and suppress metastasis and invasion of TP-expressing tumors in mice. Although the mechanism of action of D-dRib is still unknown, the physiological activities of D-dRib have recently been reported by several groups. We review the role of D-dRib in tumor progression and discuss inhibition of D-dRib as a promising approach for chemotherapy of various tumors.
Export Options
About this article
Cite this article as:
Nakajima Yuichi, Madhyastha Radha and Maruyama Masugi, 2-Deoxy-D-Ribose, a Downstream Mediator of Thymidine Phosphorylase, Regulates Tumor Angiogenesis and Progression, Anti-Cancer Agents in Medicinal Chemistry 2009; 9 (2) . https://dx.doi.org/10.2174/187152009787313846
DOI https://dx.doi.org/10.2174/187152009787313846 |
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
-
Relative In Vitro Potentials of Parthenolide to Induce Apoptosis and Cell Cycle Arrest in Skin Cancer Cells
Current Drug Discovery Technologies ADAMTS9-AS2: A Functional Long Non-coding RNA in Tumorigenesis
Current Pharmaceutical Design Population Diversity and its Relationship with Infectious and Tumor Diseases
Current Immunology Reviews (Discontinued) P53 Family: At the Crossroads in Cancer Therapy
Current Medicinal Chemistry Pharmacological Management of Psychosis in Parkinson Disease: A Review
Current Drug Therapy Current and Potential Treatments for Cervical Cancer
Current Cancer Drug Targets N-Myristoyltransferase: A Novel Target
Mini-Reviews in Medicinal Chemistry Pharmacokinetics and Systems Pharmacology of Anti-CD47 Macrophage Immune Checkpoint Inhibitor Hu5F9-G4
Current Pharmacogenomics and Personalized Medicine Measurement of CYP1A2 Activity: A Focus on Caffeine as a Probe
Current Drug Metabolism Hydrogen Sulfide Generation in Mammals: The Molecular Biology of Cystathionine-β-Synthase (CBS) and Cystathionine-γ-Lyase (CSE)
Inflammation & Allergy - Drug Targets (Discontinued) The ARRONAX Project
Current Radiopharmaceuticals Study of Cancer Cell Lines with Fourier Transform Infrared (FTIR)/ Vibrational Absorption (VA) Spectroscopy
Current Physical Chemistry Exploiting Internal Ribosome Entry Sites in Gene Therapy Vector Design
Current Gene Therapy Hapten Recognition by T Cells: A Functional and Molecular View
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Biochemical Markers of Renal Function
Current Medicinal Chemistry Follow the ATP: Tumor Energy Production: A Perspective
Anti-Cancer Agents in Medicinal Chemistry Anti-Cancer Therapies that Utilize Cell Penetrating Peptides
Recent Patents on Anti-Cancer Drug Discovery Genistein as a Potential Anticancer Agent Against Head and Neck Squamous Cell Carcinoma
Current Topics in Medicinal Chemistry Target Driven Preclinical Screening for New Antimitotic Chemotherapy Agents
Current Topics in Medicinal Chemistry Breaking the DNA Damage Response via Serine/Threonine Kinase Inhibitors to Improve Cancer Treatment
Current Medicinal Chemistry