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

SUMMARY P‐I894B inhibits prolyl hydroxylase in vitro and has been proposed as a topical treatment for dermal fibrosis. The drug had simitar 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 μg/ml but time‐dependent cell death at 1–50 μg/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 0.1–05 μg/ml, but this was clearly related to loss of viability. Collagen synthesis by monolayer cultures was unaffected at 0.05 and 0.1 μg/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.