Inhibitory Effects of Prostanoids on the Proliferation of Transformed Human Epidermal Cells in Culture

Abstract
The cytotoxic action of various prostanoids was examined on a transformed human epidermal cell line (HSC-1), and methyl(5S,6S,7Z)-5,6-diacetoxy-7-((2S)-4-chloro-2-hydroxy-2-((2Z)-2-octenyl)-5-oxo-3-cyclopentenylidene)heptanoate (YM-11), which is a punaglandin compound, was found to be most active. YM-11 exerted a dose-dependent inhibition of HSC-1 cell growth over 0.03 µM (0.01 µg/ml), and at 0.3 µM(0.1 µg/ml) its growth was completely inhibited. The IC50 value of YM-11 on HSC-1 cell growth was calculated as 0.15 µM(0.05 µg/ml). Methyl(E)-7-(5-chloro-2-hydroxy-2-octyl-5-oxo-3-cyclopentenylidene)heptanoate (YM-3), which is also a punaglandin derivative, showed remarkable cytotoxicity on HSC-1 cells with an IC50 of 0.24 µM(0.08 µg/ml). Concerning other cytotoxic prostaglandins (PGs), the IC50 values of Δ7-PGA1, Δ12-PGJ2 and PGD2 were 1.5 µM (0.5 µg/ml), 2.1 µM(0.75 µg/ml) and 5.7 µM (2 µg/ml), respectively. On the basis of the present data and previous in vitro and in vivo evidence, punaglandin derivatives may be useful antineoplastic agents for skin cancer.