Oxidative stress mediates CoCl(2)-induced prostate tumour cell adhesion: role of protein kinase C and p38 mitogen-activated protein kinase.
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).
Lu
Ning
N
Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing, China.
Zhou
Hong
H
Lin
Yan-hua
YH
Chen
Zhi-qiang
ZQ
Pan
Yan
Y
Li
Xue-jun
XJ
D002448:Cell Adhesion / Q000187:drug effects; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003035:Cobalt / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D018384:Oxidative Stress; D011471:Prostatic Neoplasms / Q000473:pathology*; D011493:Protein Kinase C / Q000096:biosynthesis*; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D003035:Cobalt; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; C018021:cobaltous chloride; C093642:SB 203580