The synthetic phosphagen cyclocreatine phosphate inhibits the growth of a broad spectrum of solid tumors.

Published

Journal Article

BACKGROUND: The brain isoform of creatine kinase (CKBB), an enzyme involved in energy metabolism, has been implicated in cellular transformation process. Cyclocreatine (CCr), a creatine kinase (CK) substrate analogue, was shown to inhibit the growth of a broad spectrum of solid tumors expressing high levels of CK. Cyclocreatine phosphate (CCrP) generated by CK, was proposed to be the active form responsible for growth inhibition. MATERIALS AND METHODS: We synthesized CCrP and tested its cellular uptake and anti tumor activity in stem cell assays and in athymic mouse models. RESULTS: CCrP seems to be taken up by cells and inhibits the growth of solid tumors with high levels of CK. CCr and CCrP have similar specificity and potency. CONCLUSION: The observation that only high-CK cell lines were responsive to CCrP, similar to CCr, indicates that the enzyme requirement was not bypassed. We propose that CK is a target for CCrP, and is involved in mediating its antiproliferative activity.

Full Text

Duke Authors

Cited Authors

  • Schimmel, L; Khandekar, VS; Martin, KJ; Riera, T; Honan, C; Shaw, DG; Kaddurah-Daouk, R

Published Date

  • January 1, 1996

Published In

Volume / Issue

  • 16 / 1

Start / End Page

  • 375 - 380

PubMed ID

  • 8615639

Pubmed Central ID

  • 8615639

International Standard Serial Number (ISSN)

  • 0250-7005

Language

  • eng

Conference Location

  • Greece