Effects of the black tea polyphenol theaflavin-2 on apoptotic and inflammatory pathways in vitro and in vivo
Article first published online: 28 JUL 2010
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 55, Issue 2, pages 198–208, February 2011
How to Cite
Gosslau, A., En Jao, D. L., Huang, M.-T., Ho, C.-T., Evans, D., Rawson, N. E. and Chen, K. Y. (2011), Effects of the black tea polyphenol theaflavin-2 on apoptotic and inflammatory pathways in vitro and in vivo. Mol. Nutr. Food Res., 55: 198–208. doi: 10.1002/mnfr.201000165
- Issue published online: 3 FEB 2011
- Article first published online: 28 JUL 2010
- Manuscript Accepted: 19 JUN 2010
- Manuscript Revised: 28 MAY 2010
- Manuscript Received: 7 APR 2010
- Commission on Science and Technology, State of New Jersey as a component of the Pioneering Nutraceutical Research Program
- NIH-NCCAM Grant. Grant Number: 1R43AT001143-01A1
Scope: Theaflavin-2 (TF-2), a major component of black tea extract, induces apoptosis of human colon cancer cells and suppresses serum-induced cyclooxygenase-2 (COX-2) expression 1. Here, we explored the mechanisms for activation of apoptosis, evaluated the impact on inflammatory genes in a broader panel of cells and tested whether topical anti-inflammatory effects could be observed in vivo.
Methods and results: TF-2 triggered apoptosis in five other transformed cancer cell lines, inducing cell shrinkage, membrane blebbing, and mitochondrial clustering within 3 h of treatment. Among a set of pro-apoptotic genes, TF-2 quickly induced the up-regulation of P53 and BAX, suggesting mitochondria as the primary target. Using a cell model for inflammatory response, we showed that TF-2 suppressed the 12-O-tetradecanoylphorbol-13-acetate-induced COX-2 gene expression, and also down-regulated TNF-α, iNOS, ICAM-1, and NFκB. A reporter gene assay showed that TF-2 down-regulated COX-2 at the transcriptional level. We also demonstrated that TF-2 exhibited anti-inflammatory activity in two mouse models of inflammation. Topical application with TF-2 significantly reduced ear edema and produced a pattern of gene down-regulation similar to that observed in the cell model.
Conclusion: These results suggest that the anti-inflammatory and pro-apoptotic activity of TF-2 may be exploited therapeutically in cancer and other diseases associated with inflammation.