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.
Duke Scholars
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- Tumor Cells, Cultured
- Prostatic Neoplasms
- Phosphocreatine
- Oncology & Carcinogenesis
- Neoplasms
- Neoplasm Transplantation
- Mice, Nude
- Mice, Inbred BALB C
- Mice
- Male
Citation
Published In
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Cells, Cultured
- Prostatic Neoplasms
- Phosphocreatine
- Oncology & Carcinogenesis
- Neoplasms
- Neoplasm Transplantation
- Mice, Nude
- Mice, Inbred BALB C
- Mice
- Male