Inhibition of topoisomerases by antitumor prostaglandins

Topoisomerase II from human placenta was strongly inhibited by prostaglandins such as delta 12,14-PGJ2, delta 12-PGJ2, PGA2, and PGA1, which have an antitumor activity. The topoisomerase II inhibitions by these prostaglandins were dose-dependent and IC50 values of delta 12,14-PGJ2, delta 12-PGJ2, PGA2, and PGA1 were 22 microM, 74 microM, 75 microM, and 98 microM, respectively. Topoisomerase I from calf thymus gland was inhibited by delta 12,14-PGJ2, delta 12-PGJ2, and PGA2, but not inhibited by other prostaglandins even at high concentrations. Only the prostaglandins having the antitumor activity inhibited topoisomerase II. The results suggest that the antitumor activity of prostaglandins may be related, at least in part, to inhibition of topoisomerase II in tumor cells.