title: Green tea polyphenol epigallocatechin-3-gallate suppresses collagen production and proliferation in keloid fibroblasts via inhibition of the STAT3-signaling pathway.
abstract: Keloids are benign skin tumors characterized by collagen accumulation and hyperproliferation of fibroblasts. To find an effective therapy for keloids, we explored the pharmacological potential of (-)-epigallocatechin-3-gallate (EGCG), a widely investigated tumor-preventive agent. When applied to normal and keloid fibroblasts (KFs) in vitro, proliferation and migration of KFs were more strongly suppressed by EGCG than normal fibroblast proliferation and migration (IC(50): 54.4 microM (keloid fibroblast (KF)) versus 63.0 microM (NF)). The level of Smad2/3, signal transducer and activator of transcription-3 (STAT3), and p38 phosphorylation is more enhanced in KFs, and EGCG inhibited phosphorylation of phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated protein kinase 1/2 (ERK1/2), and STAT3 (Tyr705 and Ser727). To evaluate the contribution of these pathways to keloid pathology, we treated KFs with specific inhibitors for PI3K, ERK1/2, or STAT3. Although a PI3K inhibitor significantly suppressed proliferation, PI3K and MEK/ERK inhibitors had a minor effect on migration and collagen production. However, a JAK2/STAT3 inhibitor and a STAT3 siRNA strongly suppressed proliferation, migration, and collagen production by KFs. We also found that treatment with EGCG suppressed growth and collagen production in the in vivo keloid model. This study demonstrates that EGCG suppresses the pathological characteristics of keloids through inhibition of the STAT3-signaling pathway. We propose that EGCG has potential in the treatment and prevention of keloids.
authors.affiliation: Department of Dermatology, School of Medicine, Korea University, Seoul, Korea.
authors.forename: Gyuman
authors.initials: G
authors.lastname: Park
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Yoon
authors.forename: Jai-Hee
authors.initials: JH
authors.lastname: Moon
authors.forename: Bona
authors.initials: B
authors.lastname: Kim
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Jun
authors.forename: Sejong
authors.initials: S
authors.lastname: Oh
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
authors.forename: Hea Joon
authors.initials: HJ
authors.lastname: Song
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Noh
authors.forename: Chilhwan
authors.initials: C
authors.lastname: Oh
authors.forename: Seungkwon
authors.initials: S
authors.lastname: You
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007627:Keloid / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008819:Mice, Nude; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D059808:Polyphenols; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013662:Tea / Q000737:chemistry; D014315:Triterpenes / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D013662:Tea; D014315:Triterpenes; D002392:Catechin; D003094:Collagen; C045651:epigallocatechin gallate; D019869:Phosphatidylinositol 3-Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C038106:cucurbitacin I