Prostaglandins in the treatment of cancer

Abstract

Prostaglandins (PGs) with antiproliferative activity against tumor cells consist of the cyclopentenone PGs and the alkylidene cyclopentenone PGs. Such PGs are PGD2, PGJ2, delta 12-PGJ2, PGA1, delta 7-PGA1, and PGA2. Both PGJ2 and delta 12-PGJ2 are ultimate metabolites of PGD2 and have potent antiproliferative activity on tumor cells. delta 12-PGJ2 was identified in human urine, whereas delta 7-PGA1 has not been found in the human body. One important characteristic of both delta 7-PGA1 and delta 12-PGJ2 is that they have little cross resistance with cisplatin and adriamycin in vitro and in vivo. delta 7-PGA1 has 5-fold greater antitumor activity than delta 12-PGJ2. Methyl ester-delta 7PGA1 (methyl-delta 7-PGA1) is stable chemically and can be easily synthesized in large amounts. All four isomers of methyl-delta 7-PGA1 showed the same antiproliferative activities on ovarian carcinoma cells. In addition, methyl-delta 7-PGA1 integrated in lipid microspheres (lipo-methyl-delta 7-PGA1) is more soluble in water than methyl-delta 7-PGA1 alone. Hence, lipo-methyl-delta 7-PGA1 was selected for extensive preclinical studies. Intravenous administration of lipo-methyl-delta 7-PGA1 could inhibit the growth of both HeLa S3 and Lovo colon cancer cells transplanted subcutaneously in nude mice. Lipo-methyl-delta 7-PGA1 by intraperitoneal administration could prolong the survival of scid mice bearing 2008C/13* cells resistant to cisplatin. The combined administration of cisplatin and lipo-methyl-delta 7-PGA1 prolonged the survival of nude mice bearing HRA cells compared with each single agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)