1. ¹Department of Dermatology, School of Medicine, Korea University, Seoul, Korea
2. ²Division of Biotechnology and Genetic Engineering, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea
3. ³Division of Animal Sciences, College of Agriculture and Life Sciences, Chonnam National University, Kwangju, Korea
4. ⁴Department of Dermatology, Gachon University of Medicine and Science, Incheon, Korea

Correspondence: Dr Seungkwon You, Division of Biotechnology and Genetic Engineering, College of Life Sciences and Biotechnology, Korea University, 1, 5-ka, Anam-dong, Sungbuk-Gu, Seoul 136-701, Korea. E-mail: bioseung@korea.ac.kr; ChilHwan Oh, Research Institute for Skin Image, Department of Dermatology, School of Medicine, Korea University, 1, 5-ka, Anam-dong, Sungbuk-Gu, Seoul 136-701, Korea. E-mail: choh@korea.ac.kr

Received 12 October 2007; Revised 25 February 2008; Accepted 7 March 2008; Published online 8 May 2008.

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 (IC₅₀: 54.4 M (keloid fibroblast (KF)) versus 63.0 M (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.