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Suppression of insulin‐like growth factor signalling pathway and collagen expression in keloid‐derived fibroblasts by quercetin: its therapeutic potential use in the treatment and/or prevention of keloids
Author(s) -
Phan T.T.,
See P.,
Tran E.,
Nguyen T.T.T.,
Chan S.Y.,
Lee S.T.,
Huynh H.
Publication year - 2003
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1046/j.1365-2133.2003.05174.x
Subject(s) - keloid , fibroblast , growth factor , cell growth , insulin like growth factor , microbiology and biotechnology , chemistry , medicine , endocrinology , biology , receptor , in vitro , biochemistry , pathology
Summary Background Keloids are characterized by abnormal proliferation of fibroblasts and overproduction of collagen. Insulin‐like growth factor (IGF)‐I is mitogenic for fibroblasts and a stimulatory factor for collagen synthesis. Objectives We have assessed the in vitro effects of quercetin on proliferation, collagen synthesis and the expression of the IGF system in keloid‐derived fibroblasts. Methods Fibroblasts were isolated from earlobe keloids and exposed to quercetin at different concentrations. The inhibitory effects of quercetin on fibroblast proliferation were assayed using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, Western and Northern blot analyses. Results Quercetin inhibited keloid fibroblast (KF) proliferation in a dose‐dependent manner. Significant growth inhibition was observed on day 2 of culture. The dose required for 50% growth inhibition was approximately 25 µg mL −1 . Collagen 1 expression was significantly decreased while collagen 3 was almost undetectable following quercetin treatment. Basal levels of IGF‐I receptor (IGF‐IR) β subunits, p85 subunit of phosphatidylinositol 3‐kinase, c‐Raf, phospho‐Raf‐1, phospho‐MEK 1/2, phospho‐mitogen‐activated protein kinase, phospho‐Elk‐1 and phospho‐Akt‐1 were significantly reduced when KF cells were exposed to quercetin for 24 h. Blocking IGF‐IR activity with IGF‐IR antibody or neutralizing endogenous IGF‐I activity with IGF‐I antibody led to significant growth inhibition suggesting the role of IGF‐I in regulation of KF proliferation. Conclusions Because the IGF system plays an important part in fibroblast cell proliferation and collagen production, the described activities of quercetin on the IGF system and collagen expression may provide a novel approach for the use of quercetin in treatment and/or prevention of hypertrophic scar and keloid.