Document Detail

Inhibition of the proliferation of transformed epidermal cells in culture by various prostaglandins.
MedLine Citation:
PMID:  2439606     Owner:  NLM     Status:  MEDLINE    
Cytotoxic action of various prostaglandins (PGs) was examined on the PAM 212 transformed mouse epidermal cell line, and delta 7-PGA1 was found most active. delta 7-PGA1 exerted a dose-dependent inhibition of PAM 212 cell growth over 0.1 microgram/ml (0.3 microM). At 1.6 microgram/ml (4.6 microM) growth was completely inhibited, and the number of viable cells decreased remarkably during culture. The concentration needed for 50% growth inhibition (IC50) value of delta 7-PGA1 on PAM 212 cell growth was calculated as 0.4 microgram/ml (1.1 microM). At this concentration, the DNA synthesis in 24- and 48-h 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 D2, a major PG in mast cells, also showed potent cytotoxic activity. However, this action was expressed as 9-deoxy-delta 9,12-13,14-dihydro-PGD2 (delta 12-PGJ2), which was converted from PGD2 in plasma, and had a 3-fold stronger growth inhibitory activity than PGD2; the IC50 values of PGD2 and delta 12-PGJ2 were 2 micrograms/ml (5.7 microM) and 0.75 microgram/ml (2.1 microM), respectively. Among other PGs tested, PGA2 showed a comparable growth inhibitory activity, and PGB2, PGE1, and PGE2 less but significant activity. Prostaglandin F2 alpha and PGI2 however, had no such effect on cell proliferation at 5 micrograms/ml (14.3 microM) concentration, suggesting that cyclopentenone structure is an essential moiety of PG derivatives for cell growth inhibition. This cytotoxic action of delta 7-PGA1 and delta 12-PGJ2 appears to be independent of cyclic-AMP, since these PGs were virtually inactive in raising intracellular cyclic-AMP levels in PAM 212 cells.
K Ikai; M Ujihara; M Kashihara; M Fukushima
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  89     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  1987 Jul 
Date Detail:
Created Date:  1987-07-28     Completed Date:  1987-07-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  69-72     Citation Subset:  IM    
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MeSH Terms
Cell Division / drug effects
Cells, Cultured
Cyclic AMP / metabolism
Cytotoxins / pharmacology
DNA / biosynthesis
Epidermis / cytology*,  metabolism
Prostaglandins / pharmacology*
Prostaglandins A, Synthetic / pharmacology
Reg. No./Substance:
0/Cytotoxins; 0/Prostaglandins; 0/Prostaglandins A, Synthetic; 60-92-4/Cyclic AMP; 68238-35-7/Keratins; 9007-49-2/DNA; 92711-55-2/9-oxo-15-hydroxy-delta 7,10,13-prostatrienoic acid methyl ester

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