Cyclocreatine inhibits stimulated motility in tumor cells possessing creatine kinase.

Journal Article

Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine), an analog of creatine and a substrate for creatine kinase (EC 2.7.3.2), inhibits the stimulated motility of tumor cells which possess creatine kinase. A2058-055 human melanoma cells, transfected with a creatine kinase gene, showed an 80-90% reduction in chemotactic response to type IV collagen when incubated overnight in the presence of 10 mM cyclocreatine (p < 0.0001 for n = 8 experiments). This inhibitory effect of cyclocreatine can be partially reversed by addition of creatine to the overnight cell treatment. Non-transfected cells, with very low levels of creatine kinase, were not significantly inhibited. Further experiments utilizing type IV collagen as attractant demonstrated that cyclocreatine inhibited the chemokinetic (91%) and the haptotactic (73%) responses and the in vitro invasion of A2058-055 cells through Matrigel-coated membranes (88%). In addition, motility stimulation of A2058-055 cells by either autotaxin or fibronectin was markedly inhibited by cyclocreatine. DU-145 prostatic tumor cells, which express endogenous creatine kinase, also have a reduced motility response to either autotaxin or epidermal growth factor induced motility in the presence of cyclocreatine.

Full Text

Duke Authors

Cited Authors

  • Mulvaney, PT; Stracke, ML; Nam, SW; Woodhouse, E; O'Keefe, M; Clair, T; Liotta, LA; Khaddurah-Daouk, R; Schiffmann, E

Published Date

  • September 1998

Published In

Volume / Issue

  • 78 / 1

Start / End Page

  • 46 - 52

PubMed ID

  • 9724093

Electronic International Standard Serial Number (EISSN)

  • 1097-0215

International Standard Serial Number (ISSN)

  • 0020-7136

Digital Object Identifier (DOI)

  • 10.1002/(sici)1097-0215(19980925)78:1<46::aid-ijc9>3.0.co;2-x

Language

  • eng