title: Lapachol suppresses cell proliferation and secretion of interleukin-6 and plasminogen activator inhibitor-1 of fibroblasts derived from hypertrophic scars.
abstract: OBJECTIVE
  The pathogenesis and therapy of hypertrophic scar have not yet been established. Our aim was to investigate the antiproliferative and antisecretory effects of lapachol, isolated from the stem bark of Avicennia rumphiana Hall. f., on hypertrophic scar fibroblasts.
  
  
  METHODS
  The effects of lapachol on hypertrophic scar fibroblast proliferation were measured using the MTT assay, cell-cycle analyses and lactate dehydrogenase assays. The type I collagen α-chain (COL1A1), interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) mRNA and/or protein levels of hypertrophic scar-fibroblasts were quantitated by real-time PCR and ELISA.
  
  
  RESULTS
  Lapachol at 25 and 50 µm significantly inhibited the in vitro proliferation of hypertrophic scar fibroblasts, but not fibroblasts from non-lesional skin sites. In addition, lapachol had no apparent effect on cell cycle and lactate dehydrogenase activity in conditioned medium from lapachol-treated hypertrophic scar fibroblasts was nearly equal to that in medium from vehicle-treated cells. Lapachol treatment also inhibited COL1A1 and PAI-1 mRNA levels in hypertrophic scar fibroblasts, but did not affect IL-6 mRNA levels. The protein levels of IL-6 and PAI-1 in conditioned medium from hypertrophic scar fibroblasts treated with 50 µm lapachol were lower than those from vehicle-treated hypertrophic scar fibroblasts.
  
  
  CONCLUSIONS
  Lapachol decreased the proliferation rate of hypertrophic scar fibroblasts. As IL-6 and PAI-1 secretion was also lowered in lapachol-treated hypertrophic scar fibroblasts, our findings suggested that lapachol may have suppressed extracellular matrix hyperplasia in wound healing and possibly alleviated the formation of hypertrophic scar.
authors.affiliation: Faculty of Pharmacy, Meijo University, Tempaku-ku, Nagoya, Japan. tmatsui@aichi-med-u.ac.jp
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsui
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ito
authors.forename: Makiko
authors.initials: M
authors.lastname: Oda
authors.forename: Masataka
authors.initials: M
authors.lastname: Itoigawa
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yokoo
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
mesh_terms: D032407:Avicennia / Q000737:chemistry; D001706:Biopsy; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D045022:Lactate Dehydrogenases / Q000378:metabolism; D009285:Naphthoquinones / Q000302:isolation & purification / Q000494:pharmacology*; D009994:Osmolar Concentration; D024301:Plant Bark / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C508600:IL6 protein, human; D015850:Interleukin-6; D009285:Naphthoquinones; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051321:SERPINE1 protein, human; C008252:lapachol; D045022:Lactate Dehydrogenases