Thymidine phosphorylase enhances reactive oxygen species generation and interleukin-8 expression in human cancer cells

Tabata,Sho; Ikeda,Ryuji; Yamamoto,Masatatu; Furukawa,Tatsuhiko; Kuramoto,Takuya; Takeda,Yasuo; Yamada,Katsushi; Haraguchi,Misako; Nishioka,Yasuhiko; Sone,Saburo; Akiyama,Shin-Ichi

doi:10.3892/or.2012.1887

Thymidine phosphorylase enhances reactive oxygen species generation and interleukin-8 expression in human cancer cells

Authors:
- 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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Affiliations: Department of Medical Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan, Department of Clinical Pharmacy and Pharmacology, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan, Department of Molecular Oncology, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan, Department of Biochemistry and Molecular Biology, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan, Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan
Published online on: June 26, 2012 https://doi.org/10.3892/or.2012.1887
Pages: 895-902

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Abstract

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.

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