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- Title
Paclitaxel Induces Vascular Endothelial Growth Factor Expression through Reactive Oxygen Species Production.
- Authors
Hyun Sun Kim; Jin Mi Oh; Dong Hoon Jin; Kyu-Hwan Yang; Eun-Yi Moon
- Abstract
The antineoplastic drug paclitaxel is known to block cells in the G2/M phase of the cell cycle through stabilization of microtubules. The development of paclitaxel resistance in tumors is one of the most significant obstacles to successful therapy. Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) are important regulators of neovascularization. HIF-1 regulates VEGF expression at the transcriptional level. Here, we investigated whether paclitaxel treatment affects VEGF expression for the development of paclitaxel resistance. Paclitaxel treatment induced dose-dependent cell death and increased VEGF expression. Paclitaxel also induced nuclear factor-κB activation and stabilized HIF-1α, which stimulated luciferase activity of HIF-1α response element on VEGF gene. As paclitaxel treatment produced reactive oxygen species (ROS), VEGF expression was increased by H2O2 treatment and reduced by various ROS scavengers such as N-acetyl-L-cysteine, pyrrolidine dithiocarbamate and diphenylene iodonium. Paclitaxel-induced cell death was aggravated by incubation with those ROS scavengers. Collectively, this suggests that paclitaxel-induced VEGF expression could be mediated by paclitaxel-induced ROS production through nuclear factor-κB activation and HIF-1α stabilization, which could affect resistance induction to antitumor therapeutics during cancer treatment. Copyright © 2008 S. Karger AG, Basel
- Subjects
PACLITAXEL; ANTINEOPLASTIC agents; REACTIVE oxygen species; HYPOXEMIA; VASCULAR endothelial growth factors; CELL cycle; MICROTUBULES
- Publication
Pharmacology, 2008, Vol 81, Issue 4, p317
- ISSN
0031-7012
- Publication type
Article
- DOI
10.1159/000119756