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Anticancer Res. 1996 Jan-Feb;16(1):375-80.

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

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  • 1Amira Inc., Cambridge, MA 02139, USA.

Abstract

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.

PMID:
8615639
[PubMed - indexed for MEDLINE]
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