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

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.