Prostate Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Prostate Cancer, including details on symptoms, genetics, screening, treatment, information.

Mechanism of 2-chloroadenosine toxicity to PC3 cell line.

Minelli A, Bellezza I, Agostini M, Bracarda S, Culig Z

Dipartimento di Medicina Sperimentale Scienze Biochimiche, Sezione Biochimica Cellulare, via del Giochetto, Perugia, Italia. albaminelli@virgilio.it

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.

Published 4 September 2006 in Prostate, 66(13): 1425-36.
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