Oxidative stress mediates CoCl(2)-induced prostate tumour cell adhesion: role of protein kinase C and p38 mitogen-activated protein kinase.

Abstract

Cobalt chloride (CoCl(2)), an agent demonstrated to stabilize hypoxia-inducible factor-1, has been associated with various hypoxic responses, and recently, some reports have linked it to increasing tumour malignancy. In this study, we observed the alteration of cell adhesion after CoCl(2) treatment and analysed the potential mechanisms responsible for such adaptations in a prostate cancer cell line PC-3 M cell. We found that CoCl(2 )increased the tumour cell adhesion in a dose-dependent manner, which correlated with reactive oxygen species (ROS) generation. When cells were incubated with the thiol reductive agent pyrrolidine dithiocarbamate (PDTC), both the ROS generation and the CoCl(2)-induced cell adhesion were abolished. Moreover, p38 mitogen-activated protein kinase (p38 MAPK) was activated in CoCl(2)-treated cells, which could be antagonized by PDTC. And when cells were pre-incubated with specific p38 MAPK inhibitor, SB203580, the cell adhesion induced by CoCl(2 )was diminished. Moreover, the protein kinase C could up-regulate cell adhesion through activating p38 MAPK. In conclusion, CoCl(2) induced ROS generation, thereby placing cells under oxidative stress and up-regulating cell adhesion; p38 MAPK and protein kinase C could be activated in a ROS-dependent fashion, which in turn contributed to cell adhesion induced by CoCl(2).

• Authors: Ning Lu, Hong Zhou, Yan-hua Lin, Zhi-qiang Chen, Yan Pan, Xue-jun Li
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 101 Issue 1 Pg. 41-6 (Jul 2007) ISSN: 1742-7835 [Print] England
• PMID: 17577315 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Imidazoles
• Pyridines
• Pyrrolidines
• Reactive Oxygen Species
• Thiocarbamates
• pyrrolidine dithiocarbamic acid
• Cobalt
• Protein Kinase C
• p38 Mitogen-Activated Protein Kinases
• cobaltous chloride
• SB 203580

Topics

• Cell Adhesion (drug effects)
• Cell Hypoxia
• Cell Line, Tumor
• Cobalt (toxicity)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (pharmacology)
• Humans
• Imidazoles (pharmacology)
• Male
• Oxidative Stress
• Prostatic Neoplasms (pathology)
• Protein Kinase C (biosynthesis)
• Pyridines (pharmacology)
• Pyrrolidines (pharmacology)
• Reactive Oxygen Species (metabolism)
• Thiocarbamates (pharmacology)
• p38 Mitogen-Activated Protein Kinases (biosynthesis)