H2O2 scavenging inhibits G1/S transition by increasing nuclear levels of p27KIP1

• Published in: Cancer letters Vol. 305; no. 1; pp. 58 - 68
• Main Authors: Ibañez, Irene L, Policastro, Lucía L, Tropper, Ivanna, Bracalente, Candelaria, Palmieri, Mónica A, Rojas, Paola A, Molinari, Beatriz L, Durán, Hebe
• Format: Journal Article
• Language: English
• Published: Ireland 01.06.2011
• Subjects: Active Transport, Cell Nucleus - drug effects; Animals; Blotting, Western; Catalase - pharmacology; Cell Line, Tumor; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cyclin D1 - metabolism; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Female; Fluorescent Antibody Technique; Free Radical Scavengers - pharmacology; G1 Phase - drug effects; Hydrogen Peroxide - metabolism; Mice; Mice, Inbred SENCAR; Mice, Nude; Reactive Oxygen Species; S Phase - drug effects
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2011.02.026

The aim of the present study was to evaluate cell cycle regulation by scavenging H(2)O(2) in tumor cells. A significant arrest in the G1 phase of the cell cycle was demonstrated in CH72-T4 carcinoma cells exposed to catalase, associated with a decrease in cyclin D1 and an increase in the CDK inhibitory protein p27(KIP1). Moreover, we found a differential intracellular distribution of p27(KIP1), which remained in the nucleus after catalase treatment. In vivo experiments showed an increase in nuclear levels of p27(KIP1) associated with the inhibition of tumor growth by H(2)O(2) scavenging, confirming in vitro results. To conclude, H(2)O(2) scavenging may induce cell cycle arrest through the modulation of cyclin D1 and p27(KIP1) levels and nuclear localization of p27(KIP1). To our knowledge, this is the first report that demonstrates that the modulation of ROS alters the intracellular localization of a key regulatory protein of G1/S transition.