Creatine kinase (CK) an
enzyme involved in cellular
ATP homeostasis has been implicated in
tumorigenesis.
Cyclocreatine (CCr) a CK substrate analog was shown to be cytotoxic to a broad spectrum of solid
tumors. We have measured and compared the CK activity and CCr sensitivity of 49 transformed and non-transformed cell lines. Among tumor cell lines, there was a strong correlation between the two (p = 0.0026, regression analysis); cell lines expressing high levels of CK (>0.10 Units/mg
protein) were generally sensitive to the
drug and cell lines with low CK were resistant. Tumor cell lines highest in CK and most sensitive to CCr were derived from prostate, small cell lung and neuronal tissue. The hematopoetic
tumor lines tested were generally low in CK and all were resistant to CCr. Fourteen non-transformed cell lines were examined and all were resistant to the compound, including six with high levels of CK. Thus, CCr preferentially targeted
tumor cells. Further, CCr inhibited
tumor cell proliferation more efficiently than macromolecular synthesis indicating that, rather than exerting a general effect on energy metabolism, CCr may act on a specific pathway involved in controlling
tumor cell proliferation.