Suppressive effects of various antitumor prostaglandin derivatives on the activity levels of DNA polymerases in human cultured tumor cells.
Some PG derivatives have been shown to be inhibitory for tumor cell growth. To elucidate the underlying mechanism(s) for this, we examined various DNA polymerase activities in PG-treated cultured cells. Human KBIII cells were exposed for one day to each of PGJ2, delta 7-PGA1 and delta 12-PGJ2 at a concentration of 5 micrograms/ml. The cells were harvested and homogenized, and the cell-free extracts were analyzed by phosphocellulose column chromatography for separation, identification, and quantification of each of the DNA polymerases. The results obtained were as follows: The activity of DNA polymerase alpha, which is responsible for DNA replication, has remained almost unchanged by any of the PG derivatives tested (77-87%), whereas the activity of DNA polymerase beta (repair enzyme) was found to dramatically decrease to 13 to 20% of that of the nontreated control cells by treatment with any of these PG derivatives. The results indicate that (a) these PG derivatives inhibit, either directly or indirectly, the synthesis of DNA polymerase beta in the KBIII cell, and (b) DNA polymerase beta may also participate in DNA replication other than DNA repair.
D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D019384:Nucleic Acid Synthesis Inhibitors; D015230:Prostaglandin D2 / Q000031:analogs & derivatives; D011455:Prostaglandins A, Synthetic / Q000494:pharmacology; D011457:Prostaglandins D / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019384:Nucleic Acid Synthesis Inhibitors; D011455:Prostaglandins A, Synthetic; D011457:Prostaglandins D; D011465:Prostaglandins, Synthetic; C037112:9-deoxy-delta-9-prostaglandin D2; C040810:9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydroprostaglandin D2; C048481:9-oxo-15-hydroxy-delta 7,10,13-prostatrienoic acid methyl ester; D015230:Prostaglandin D2