Molecular Basis for the Inhibition of Anticancer Agents-induced Apoptosis by Thymidine Phosphorylase
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- IKEDA Ryuji
- Department of Clinical Pharmacy, Kagoshima University Hospital
Bibliographic Information
- Other Title
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- 抗がん剤で誘導されるアポトーシスのチミジンホスホリラーゼによる抑制機構
- コウガンザイ デ ユウドウサレル アポトーシス ノ チミジン ホスホリラーゼ ニ ヨル ヨクセイ キコウ
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Abstract
An angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. 2-Deoxy-D-ribose, a degradation product of thymidine generated by TP enzymatic activity, partially prevented hypoxia-induced apoptosis. TP was expressed at higher levels in tumor tissues compared to the adjacent non-neoplastic tissues in a variety of human carcinomas. High expression of TP is associated with an unfavorable prognosis. To investigate the effect of TP on cisplatin-induced apoptosis, human leukemia Jurkat cells were transfected with wild-type or mutant (L148R) TP cDNA. Jurkat cells transfected with TP cDNA (Jurkat/TP) and mutant TP cDNA (Jurkat/TPMu) expressed high levels of TP, while Jurkat/CV cells which were transfected with a control vector did not express TP. A high TP enzyme activity was detected in Jurkat/TP cells, but not in Jurkat/CV and Jurkat/TPMu cells. Sensitivities to cisplatin of these cells were determined by MTT assay. IC50 values for cisplatin of Jurkat/CV, Jurkat/TP, and Jurkat/TPMu cells were 4.50, 14.08, 13.40 μM, respectively. Jurkat/TP and Jurkat/TPMu cells were about three times more resistant to cisplatin than Jurkat/CV cells. TP inhibited activation of caspase 3, 9 and mitochondrial cytochrome c release induced by cisplatin. These findings suggest a mechanism by which TP confers the resistance to cisplatin-induced apoptosis. Moreover, mutant TP that has no enzymatic activity also suppressed the cisplatin-induced apoptosis. These suggest that TP molecules have cytoprotective functions against cytotoxic agents.<br>
Journal
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- YAKUGAKU ZASSHI
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YAKUGAKU ZASSHI 127 (7), 1097-1102, 2007
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390282681104730368
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- NII Article ID
- 110006318158
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- NII Book ID
- AN00284903
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- COI
- 1:STN:280:DC%2BD2szos1eqsw%3D%3D
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- ISSN
- 13475231
- 00316903
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- NDL BIB ID
- 8881952
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed