2-Deoxy-D-Ribose, a Downstream Mediator of Thymidine Phosphorylase, Regulates Tumor Angiogenesis and Progression

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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2-Deoxy-D-Ribose, a Downstream Mediator of Thymidine Phosphorylase, Regulates Tumor Angiogenesis and Progression



Anti-Cancer Agents in Medicinal Chemistry, 9(2): 239-245.

Author(s): Yuichi Nakajima, Radha Madhyastha and Masugi Maruyama.

Affiliation: Department of Applied Physiology, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake-cho, Miyazaki 8891692, Japan.

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.



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Article Details

Volume: 9
Issue Number: 2
First Page: 239
Last Page: 245
Page Count: 7
DOI: 10.2174/187152009787313846
Price: $58
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