title: Thymidine phosphorylase enhances reactive oxygen species generation             and interleukin-8 expression in human cancer cells.
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.
authors: Department of Medical Oncology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
authors: Sho
authors: S
authors: Tabata
authors: Ryuji
authors: R
authors: Ikeda
authors: Masatatu
authors: M
authors: Yamamoto
authors: Tatsuhiko
authors: T
authors: Furukawa
authors: Takuya
authors: T
authors: Kuramoto
authors: Yasuo
authors: Y
authors: Takeda
authors: Katsushi
authors: K
authors: Yamada
authors: Misako
authors: M
authors: Haraguchi
authors: Yasuhiko
authors: Y
authors: Nishioka
authors: Saburo
authors: S
authors: Sone
authors: Shin-Ichi
authors: S
authors: Akiyama
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D045744:Cell Line, Tumor; D016166:Free Radical Scavengers / Q000494:pharmacology; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013939:Thymidine Phosphorylase / Q000378:metabolism*
chemical_list: D016166:Free Radical Scavengers; D016209:Interleukin-8; D017382:Reactive Oxygen Species; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D013939:Thymidine Phosphorylase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D000111:Acetylcysteine