Inhibition of Topoisomerases by Antitumor Prostaglandins.

Abstract

  Topoisomerase II from human placenta was strongly inhibited by prostaglandins such as Δ^12,14-PGJ₂, Δ¹²-PGJ₂, PGA₂, and PGA₁, which have an antitumor activity. The topoisomerase II inhibitions by these prostaglandins were dose-dependent and IC₅₀ values of Δ^12,14-PGJ₂, Δ¹²-PGJ₂, PGA₂, and PGA₁ were 22 μM, 74 μM, 75 μM, and 98 μM, respectively. Topoisomerase I from calf thymus gland was inhibited by Δ^12,14-PGJ₂, Δ¹²-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.