"Thymineless" death in androgen-independent prostatic cancer cells.
The molecular mechanism of "thymineless" death induced by 5-fluorodeoxyuridine or trifluorothymidine, in androgen-independent rat prostatic adenocarcinoma AT-3 cells was investigated. Fragmentation of genomic DNA into discrete multiples of a nucleosomal unit (i.e. 180bp subunit) and induction of expression of TRPM-2, a programmed cell death-associated gene, temporally correlated with the activation of programmed cell death in this system. In contrast, killing of AT-3 cells by osmotic lysis, or membrane-targeted metabolic inhibitors results in neither the stereotypic DNA fragmentation into nucleosomal oligomers nor the elevation of TRPM-2 mRNA levels but to non-specific biochemical changes characteristic of necrosis. These results suggest that androgen-independent prostatic cancer cells retain a major portion of the programmed cell death cascade which can be activated by non-androgen ablative cytotoxic drugs that induce "thymineless" death.
Kyprianou
N
N
Johns Hopkins Oncology Center, Baltimore, Maryland 21205.
Isaacs
J T
JT
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D005467:Floxuridine / Q000494:pharmacology*; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008297:Male; D009693:Nucleic Acid Hybridization; D010042:Ouabain / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D013936:Thymidine; D013941:Thymine / Q000378:metabolism*; D014271:Trifluridine / Q000494:pharmacology*
D004273:DNA, Neoplasm; D007461:Iodoacetates; D005467:Floxuridine; D010042:Ouabain; D013941:Thymine; D014271:Trifluridine; D013936:Thymidine; D019807:Iodoacetic Acid