Toxicity of the anthraquinone glycoside P-1894B for human skin fibroblasts.

Abstract

P-1894B inhibits prolyl hydroxylase in vitro and has been proposed as a topical treatment for dermal fibrosis. The drug had similar effects on two fibroblast lines from normal human skin and one line from a patient with lichen sclerosus et atrophicus. Exposure of logarithmically-growing cell monolayers for 72 h caused dose-dependent inhibition of proliferation at 0.05-0.5 microgram/ml but time-dependent cell death at 1-50 micrograms/ml. The epithelial cell line NCTC 2544 gave a similar result. Collagen lattices containing normal fibroblasts contracted more slowly in the presence of the drug at 0.1-0.5 microgram/ml, but this was clearly related to loss of viability. Collagen synthesis by monolayer cultures was unaffected at 0.05 and 0.1 microgram/ml P-1894B in one line of normal fibroblasts, but was reduced by 40% and 15%, respectively, in the other. The concentrations of P-1894B reported to be active against prolyl hydroxylase are therefore lethal to cultured skin cells. Although the effective use of dithranol as a topical anti-psoriatic agent, despite its cytotoxicity in vitro, is encouraging for P-1894B, further toxicological studies are imperative.

• Authors: G C Priestley
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 117 Issue 1 Pg. 67-72 (Jul 1987) ISSN: 0007-0963 [Print] England
• PMID: 2820462 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthraquinones
• vineomycin A1
• Collagen
• Procollagen-Proline Dioxygenase

Topics

• Anthraquinones (toxicity)
• Cell Division (drug effects)
• Cell Line
• Collagen (biosynthesis)
• Dose-Response Relationship, Drug
• Fibroblasts (drug effects)
• Humans
• Procollagen-Proline Dioxygenase (antagonists & inhibitors)
• Skin (cytology, drug effects, metabolism)
• Skin Diseases (metabolism)