The direct effect of continuous exposure to
prostaglandins on the cloning efficiency and proliferative capacity of human
malignant melanoma colony-forming cells in soft
agar was evaluated.
Prostaglandin A1 (
PGA1) and
prostaglandin E1 (
PGE1) effected a dose-dependent inhibition of colony formation and proliferative capacity.
PGA1 at a concentration of 5 microgram/ml reduced colony formation of cells from human
melanoma cell strains C8054, C8130, and C822 by at least 85%.
PGA1 also inhibited colony formation of cells obtained directly from biopsies of
melanoma tissues from eight patients by greater than 70% at a concentration of 5 microgram/ml. A steep dose-response curve was evident by the little effect of
PGA1 on colony formation at a concentration of 0.5 microgram/ml. The mean 50% inhibitory doses for
PGA1 and
PGE1 were 1.25 and 4.25 microgram/ml, respectively.
Prostaglandin A2 was much less effective than
PGA1 in inhibiting
melanoma colony formation. The related
prostaglandins (
prostaglandin B1,
prostaglandin F1 alpha, and
prostaglandin E2 alpha) had little or no effect on colony formation. Overall, these results suggested that the presence of a carbonyl group at position 9 of the
cyclopentane ring may be required for inhibitory activity as
prostaglandins of the A and E series inhibited human
melanoma cell growth.
PGA1 and
PGE1 did not effect a rise in cyclic
adenosine 3':5'-monophosphate levels in C8054 and C8130 cells. However, while
alpha-melanocyte-stimulating hormone and
prostaglandin F2 alpha did generate a rise in
adenosine 3':5'-monophosphate levels in C8054 cells, these
hormones had no effect on colony formation. These results are consistent with the notion that the
PGA1 and
PGE1 inhibition of
melanoma colony-forming cells occurs via a noncyclic
nucleotide mechanism.