Toxicity of the anthraquinone glycoside P-1894B for human skin fibroblasts.
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.
Priestley
G C
GC
University Department of Dermatology, Royal Infirmary, Edinburgh, U.K.
D000880:Anthraquinones / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors*; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012871:Skin Diseases / Q000378:metabolism
D000880:Anthraquinones; C032958:vineomycin A1; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase