Epigallocatechin-3-gallate induces cell apoptosis of human chondrosarcoma cells through apoptosis signal-regulating kinase 1 pathway
Article first published online: 18 APR 2011
Copyright © 2011 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 112, Issue 6, pages 1601–1611, June 2011
How to Cite
Yang, W.-H., Fong, Y.-C., Lee, C.-Y., Jin, T.-R., Tzen, J. T., Li, T.-M. and Tang, C.-H. (2011), Epigallocatechin-3-gallate induces cell apoptosis of human chondrosarcoma cells through apoptosis signal-regulating kinase 1 pathway. J. Cell. Biochem., 112: 1601–1611. doi: 10.1002/jcb.23072
- Issue published online: 18 APR 2011
- Article first published online: 18 APR 2011
- Accepted manuscript online: 16 FEB 2011 12:00AM EST
- Manuscript Accepted: 8 FEB 2011
- Manuscript Received: 22 NOV 2010
- National Science Council of Taiwan. Grant Number: NSC99-2320-B-039-003-MY3
- China Medical University Beigang Hospital. Grant Number: CMUBH R990008
- Chinese herb;
Chondrosarcoma is a malignant primary bone tumor that responds poorly to both chemotherapy and radiation therapy. (-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been shown to inhibit tumorigenesis and cancer cell growth in animal models. The aim of this study was to elucidate the mechanism of EGCG-induced apoptosis of human chondrosarcoma cells. EGCG induced cell apoptosis in human chondrosarcoma cell lines but not primary chondrocytes. EGCG induced upregulation of Bax and Bak, downregulation of Bcl-2 and Bcl-XL, and dysfunction of mitochondria in chondrosarcoma. We also found that the accumulation of reactive oxygen species (ROS) is a critical mediator in EGCG-induced cell death. EGCG induced apoptosis signal-regulating kinase 1 (ASK1) dephosphorylation and its dissociation from 14-3-3. Treatment of chondrosarcoma cells with EGCG induced p38 and c-jun-NH2-kinase (JNK) phosphorylation. Transfection with ASK1 siRNA or p38 and JNK mutant antagonized the EGCG-induced cell apoptosis. Therefore, EGCG triggered ROS and activated the ASK1-p38/JNK pathway, resulting chondrosarcoma cell death. Importantly, animal studies revealed a dramatic reduction in tumor volume after 24 days of treatment. Thus, EGCG may be a novel anti-cancer agent for the treatment of chondrosarcoma. J. Cell. Biochem. 112: 1601–1611, 2011. © 2011 Wiley-Liss, Inc.