Inhibitory properties of antitumor prostaglandins against topoisomerases.
Prostaglandins (PGs) having antitumor activity such as delta12,14-PGJ2, delta12-PGJ2, PGA2 and PGA1 strongly inhibited topoisomerase II (topo II) from human placenta, the potential order of inhibitory activity of the PGs resembling that of the antitumor activity. PGs having no antitumor activity did not inhibit topo II. Delta12,14-PGJ2 to be a potent inhibitor showed inhibitions to some extent against topo I from wheat germ, NIH3T3 and calf thymus gland, and showed no inhibition against the enzymes from Vero, A549, HeLa and COLO 201 cells. Delta12,14-PGJ2 differentially inhibited topo I from different sources. Delta12,14-PGJ2 was a topo inhibitor of the cleavable complex-nonforming type without DNA intercalation.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000494:pharmacology; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004996:Ethidium / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D051379:Mice; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D011454:Prostaglandins A / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D011454:Prostaglandins A; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C037112:9-deoxy-delta-9-prostaglandin D2; D005047:Etoposide; D004317:Doxorubicin; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D004996:Ethidium; D015230:Prostaglandin D2; D002166:Camptothecin