Inhibitory effects of prostanoids on the proliferation of transformed human epidermal cells in culture.
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-((2 Z+ ++)-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 microM (0.01 micrograms/ml), and at 0.3 microM (0.1 micrograms/ml) its growth was completely inhibited. The IC50 value of YM-11 on HSC-1 cell growth was calculated as 0.15 microM (0.05 micrograms/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 microM (0.08 micrograms/ml). Concerning other cytotoxic prostaglandins (PGs), the IC50 values of delta 7-PGA1, delta 12-PGJ2 and PGD2 were 1.5 microM (0.5 micrograms/ml), 2.1 microM (0.75 micrograms/ml) and 5.7 microM (2 micrograms/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.
Ikai
K
K
Department of Dermatology, Kyoto University Faculty of Medicine, Japan.
Sone
R
R
Fukushima
M
M
D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects*; D006801:Humans; D011453:Prostaglandins / Q000633:toxicity*
D011453:Prostaglandins