title: Mechanism of 2-chloroadenosine toxicity to PC3 cell line.
abstract: 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.
authors.affiliation: Dipartimento di Medicina Sperimentale Scienze Biochimiche, Sezione Biochimica Cellulare, via del Giochetto, Perugia, Italia. albaminelli@virgilio.it
authors.forename: Alba
authors.initials: A
authors.lastname: Minelli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bellezza
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Agostini
authors.forename: Sergio
authors.initials: S
authors.lastname: Bracarda
authors.forename: Zoran
authors.initials: Z
authors.lastname: Culig
mesh_terms: D015762:2-Chloroadenosine / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D004273:DNA, Neoplasm; D015762:2-Chloroadenosine