Effects of minoxidil on cultured human skin fibroblasts.
Two important findings related to the effect of minoxidil on human skin fibroblasts in culture are reviewed. Treatment of cells with minoxidil is associated with a specific loss of lysyl hydroxylase activity; this loss occurs gradually and is reversed by removing minoxidil from the culture medium. Experiments with inhibitors of protein and RNA synthesis reveal that minoxidil may inhibit the synthesis of lysyl hydroxylase by acting at the transcriptional level. Treatment of cells with minoxidil is also associated with inhibition of proliferation, without any sign of cytotoxicity. This effect of minoxidil is accompanied by inhibition of DNA synthesis. Since collagen is the major product of fibroblast activity and lysyl hydroxylase catalyzes a crucial reaction in collagen biosynthesis, the combined effects of minoxidil offer the potential for its use as an antifibrotic agent. Thus, minoxidil may prove to be beneficial in treating skin conditions associated with collagen accumulation.
Pinnell
S R
SR
Department of Medicine, Duke University Medical Center, Durham, N.C.
Murad
S
S
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008914:Minoxidil / Q000494:pharmacology*; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
D008914:Minoxidil; D004247:DNA; D011393:Procollagen-Proline Dioxygenase; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase