期刊
PROSTATE
卷 66, 期 13, 页码 1425-1436出版社
WILEY
DOI: 10.1002/pros.20458
关键词
2-CADO; prostate cancer; ribo-/deoxy-ribonucleotides; DNA biosynthesis enzymes
BACKGROUND. 2-CADO inhibits the growth of several types of cells and causes apoptosis by a mechanism which involves adenosine receptors or cellular uptake or both. METHODS. Androgen-independent (PC3) prostate cancer cells were used in the study and proliferation, cell-cycle progression, and apoptosis analyzed. Deoxy-and ribonucleoside triphosphate pools were determined by HPLC. The molecular mechanism was examined by assessing the involvement of DNA synthesizing enzymes in the cellular response. RESULTS. 2-CADO treatment dramatically reduced the number of prostate cancer cells and permanently stopped cell-cycle progression in the S-phase. The role of 2-CADO in prostate cancer cells is uptake-mediated and followed by sequential phosphorylations to 2-Cl-ATP that irreversibly inhibits several key-enzymes for DNA biosynthesis. CONCLUSIONS. Arrest of DNA synthesis responsible for toxicity of 2-CADO to PC3 cells is due to the lack of substrates for DNA polymerization caused by irreversible inhibition of purine/pyrimidine ribo-and 2-deoxyribonucleotides salvage enzymes.
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