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)