Abstract |
In an effort to investigate the role of creatine kinase and its substrates in malignancy we have tested the effect of cyclocreatine [1-carboxymethyl-2-iminoimidazolidine (CCr)] on the growth of tumor cells in vitro and in vivo. CCr is phosphorylated by creatine kinase to yield a synthetic phosphagen [( N-phosphorylcyclocreatine (CCr approximately P)] with thermodynamic and kinetic properties distinct from those of creatine phosphate. We show that CCr accumulates as CCr approximately P in tumor cells expressing a high level of creatine kinase, and that the accumulation of this phosphagen is detrimental to tumor cell growth. Tumor cell lines expressing a low level of creatine kinase accumulate much less CCr approximately P, and consequently are growth inhibited only at higher concentrations of CCr. When these resistant cells are transfected with a creatine kinase B expression vector, they express creatine kinase, accumulate CCr approximately P, and are growth inhibited. In vivo, in nude mouse xenografts, the rate of growth of a high creatine kinase expressing tumor cell line is inhibited in animals fed 1% CCr. Our results indicate that CCr inhibits the growth of tumor cells in vitro and in vivo.
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Authors | J W Lillie, M O'Keefe, H Valinski, H A Hamlin Jr, M L Varban, R Kaddurah-Daouk |
Journal | Cancer research
(Cancer Res)
Vol. 53
Issue 13
Pg. 3172-8
(Jul 01 1993)
ISSN: 0008-5472 [Print] United States |
PMID | 8319226
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Imidazolidines
- Isoenzymes
- Phosphocreatine
- phosphocyclocreatine
- cyclocreatine
- Creatinine
- Creatine Kinase
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Cell Division
(drug effects, physiology)
- Cell Line
- Cell Transformation, Neoplastic
- Creatine Kinase
(metabolism, physiology)
- Creatinine
(analogs & derivatives, pharmacology)
- Female
- Humans
- Imidazolidines
- Isoenzymes
- Male
- Mice
- Mice, Nude
- Neoplasms
(drug therapy, enzymology, pathology)
- Neoplasms, Experimental
(drug therapy, enzymology, pathology)
- Phosphocreatine
(analogs & derivatives, pharmacokinetics, physiology)
- Transplantation, Heterologous
- Tumor Cells, Cultured
- Uterine Cervical Neoplasms
(drug therapy, enzymology, pathology)
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