Inhibition of Topoisomerases by Antitumor Prostaglandins

• Published in: Bioscience, biotechnology, and biochemistry Vol. 62; no. 10; pp. 2073 - 2075
• Main Authors: SUZUKI, Keitarou, SHONO, Fumiko, UYEDA, Masaru
• Format: Journal Article
• Language: English
• Published: Tokyo Japan Society for Bioscience, Biotechnology, and Agrochemistry 1998; Japan Society for Bioscience Biotechnology and Agrochemistry; Oxford University Press
• Subjects: Antineoplastic agents; Antineoplastic Agents - pharmacology; antitumor; Biological and medical sciences; Enzyme Inhibitors - pharmacology; Female; General aspects; Humans; inhibition; Inhibitory Concentration 50; Medical sciences; Pharmacology. Drug treatments; Placenta - enzymology; prostaglandin; Prostaglandins - pharmacology; topoisomerase; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors; Antineoplastic agent; DNA topoisomerase (ATP-hydrolysing); Isomerases; Enzyme; Enzyme inhibitor; Prostaglandin A2; In vitro; Prostaglandin A1; Biological activity
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1271/bbb.62.2073

Topoisomerase II from human placenta was strongly inhibited by prostaglandins such as Δ 12,14 -PGJ 2 , Δ 12 -PGJ 2 , PGA 2 , and PGA 1 , which have an antitumor activity. The topoisomerase II inhibitions by these prostaglandins were dose-dependent and IC 50 values of Δ 12,14 -PGJ 2 , Δ 12 -PGJ 2 , PGA 2 , and PGA 1 were 22 μM, 74 μM, 75 μM, and 98 μM, respectively. Topoisomerase I from calf thymus gland was inhibited by Δ 12,14 -PGJ 2 , Δ 12 -PGJ 2 , and PGA 2 , 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.