Original Article
Inhibition of the Proliferation of Transformed Epidermal Cells in Culture by Various Prostaglandins

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Cytotoxic action of various prostaglandins (PGs) was examined on the PAM 212 transformed mouse epidermal cell line, and Δ7-PGA1 was found most active. Δ7-PGA1 exerted a dose-dependent inhibition of PAM 212 cell growth over 0.1 μg/ml (0.3 μM). At 1.6 μg/mI (4.6 μM) growth was completely inhibited, and the number of viable cells decreased remarkably during culture. The concentration needed for 50% growth inhibition (IC50) value of Δ7-PGA1 on PAM 212 cell growth was calculated as 0.4 μg/mI (1.1 μM). At this concentration, the DNA synthesis in 24- and 48-b cultured cells was decreased to a half of the level in the control cells, and microscopically, remaining cells showed degenerative changes with many vacuoles in their cytoplasm. Prostaglandin D1, a major PG in mast cells, also showed potent cytotoxic activity. However, this action was expressed as 9-deoxy-Δ9.12- 13, 14-dihydro-PG112-PGJ1), which was converted from PGD2 in plasma, and had a 3- fold stronger growth inhibitory activity than PGD2 the IC50, values of PGD2 and Δ12 -PGJ2 were 2 μg/mI (5.7 μM) and 0.75 μg/ml (2.1 μM), respectively. Among other PGs tested, PGA2 showed a comparable growth inhibitory activity, and PGB2, PGE1, and PGE2 less but significant activity. Prostaglandin F and PGI2 however, had no such effect on cell proliferation at 5 μg/ml (14.3 μM) concentration, suggesting that cyclopentenone structure is an essential moiety of PG derivatives for cell growth inhibition. This cytotoxic action of Δ7-PGA1 and Δ12-PGJ2 appears to be independent of cyclic-AMP, since these PGs were virtually inactive in raising intracellular cyclic-AMP levels in PAM 212 cells.

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