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Thymidine phosphorylase enhances reactive oxygen species generation and interleukin-8 expression in human cancer cells.
MedLine Citation:
PMID:  22751949     Owner:  NLM     Status:  Publisher    
Thymidine phosphorylase (TP) is an angiogenic factor that plays a pivotal role in tumor angiogenesis. Various kinds of solid tumors express TP and high TP activity is correlated with microvessel density. We have previously reported that TP enhances interleukin-8 (IL-8) expression in KB human epidermoid carcinoma cells. In this study, TP was shown to be involved in enhanced expression of IL-8 in EJ human bladder cancer cells and Yumoto human cervical cancer cells as well as KB human epidermoid carcinoma cells. The enzymatic activity of TP was required for the enhanced expression of IL-8. A degradation product of thymidine was implicated in the enhanced expression of IL-8. TP augmented reactive oxygen species (ROS) generation in KB and Yumoto cells, and the enzymatic activity of TP was again required for the generation of ROS. An antioxidant, N-acetylcysteine (NAC), attenuated the generation of ROS and IL-8 mRNA expression in KB and Yumoto cells, and H2O2 increased IL-8 mRNA expression in Yumoto cells, suggesting that ROS generated by TP caused the increased expression of IL-8 mRNA. Since TP also reduced cellular glutathione levels and transcription of γ-GCS in KB cells, the TP-induced augmentation of ROS may be partially attributed to the decreased glutathione. Our findings suggest that thymidine-derived sugars enhanced ROS generation and consequently increased IL-8 expression.
Sho Tabata; Ryuji Ikeda; Masatatu Yamamoto; Tatsuhiko Furukawa; Takuya Kuramoto; Yasuo Takeda; Katsushi Yamada; Misako Haraguchi; Yasuhiko Nishioka; Saburo Sone; Shin-Ichi Akiyama
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-26
Journal Detail:
Title:  Oncology reports     Volume:  -     ISSN:  1791-2431     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-7-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Medical Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
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