Skip to main content

Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors.

Publication ,  Journal Article
Lillie, JW; O'Keefe, M; Valinski, H; Hamlin, HA; Varban, ML; Kaddurah-Daouk, R
Published in: Cancer Res
July 1, 1993

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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

July 1, 1993

Volume

53

Issue

13

Start / End Page

3172 / 3178

Location

United States

Related Subject Headings

  • Uterine Cervical Neoplasms
  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Phosphocreatine
  • Oncology & Carcinogenesis
  • Neoplasms, Experimental
  • Neoplasms
  • Mice, Nude
  • Mice
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lillie, J. W., O’Keefe, M., Valinski, H., Hamlin, H. A., Varban, M. L., & Kaddurah-Daouk, R. (1993). Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors. Cancer Res, 53(13), 3172–3178.
Lillie, J. W., M. O’Keefe, H. Valinski, H. A. Hamlin, M. L. Varban, and R. Kaddurah-Daouk. “Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors.Cancer Res 53, no. 13 (July 1, 1993): 3172–78.
Lillie JW, O’Keefe M, Valinski H, Hamlin HA, Varban ML, Kaddurah-Daouk R. Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors. Cancer Res. 1993 Jul 1;53(13):3172–8.
Lillie JW, O’Keefe M, Valinski H, Hamlin HA, Varban ML, Kaddurah-Daouk R. Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits growth of a broad spectrum of cancer cells derived from solid tumors. Cancer Res. 1993 Jul 1;53(13):3172–3178.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

July 1, 1993

Volume

53

Issue

13

Start / End Page

3172 / 3178

Location

United States

Related Subject Headings

  • Uterine Cervical Neoplasms
  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Phosphocreatine
  • Oncology & Carcinogenesis
  • Neoplasms, Experimental
  • Neoplasms
  • Mice, Nude
  • Mice
  • Male