Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014:36:195-221.
doi: 10.1016/B978-0-12-802215-3.00010-0.

Effects of Tea Catechins on Cancer Signaling Pathways

Chung S Yang  1 , Hong Wang  2 , Jayson X Chen  2 , Jinsong Zhang  3
Affiliations

Effects of Tea Catechins on Cancer Signaling Pathways

Chung S Yang et al. Enzymes. 2014.

Abstract

The inhibitory activities of tea catechins against carcinogenesis and cancer cell growth have been demonstrated in a large number of laboratory studies. Many mechanisms for modulating cancer signaling and metabolic pathways have been proposed based on numerous studies in cell lines with (-)-epigallocatechin-3-gallate, the most abundant and active tea catechin. Nevertheless, the molecular basis for the proposed mechanisms and whether these mechanisms indeed contribute to the anticancer activities in vivo are not clearly known. This chapter reviews the basic redox properties of tea catechins, their binding to key enzymes and signal transduction proteins, and other mechanisms that lead to suppression of cell proliferation, increased apoptosis, and inhibition of angiogenesis. More weight is put on studies in vivo over experiments in vitro. It also discusses key issues involved in extrapolating results from cell line studies to mechanistic insights in vivo.

Keywords: Animal models; Cancer signaling; Cell lines; EGCG; Tea catechins.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Structures of (−)-epigallocatechin-3-gallate (EGCG) and other tea catechins. For (−)-epicatechin-3-gallate (ECG), the “OH” at 3´-position is replace by “H”; for (−)-epigallocatechin (EGC), the “gallate” at 3-position is replaced by “OH”; for (−)-epicatechin (EC), the “OH” at 3´-position is replaced by “H” and “gallate” at 3-position is replaced by “OH”.
Figure 2
Figure 2
Possible targets for the cancer preventive activity of EGCG. Some of these are direct binding targets; others are affected indirectly. The reported effective concentrations, in IC50, Ki (inhibition constant) or Kd (dissociation constant) are shown in μM. All these are from studies in vitro. When two values are given, the first value is from cell-free systems and the second value is from studies in cell lines.
Figure 3
Figure 3
Possible mechanisms of inhibition of receptor tyrosine kinases by EGCG. Epidermal growth factor receptor (EGFR) is used as an example to illustrate the multiple intra-cellular processes in signaling. 1) Upon epidermal growth factor (EGF) binding, 2) the receptor undergoes autophosphorylation and conformational changes, transforming the EGFR to the active form on the surface of cytoplasma membrane. 3) Once activated, EGFR is in a functional membrane with unique lipid composition or mobility (often referred to as lipid raft). 4) Such a functional lipid unit of EGFR, mediated by Clathrin, internalizes and the active EGFR signaling is transduced by the activation of downstream PI3K/AKT and SOS/RAS/ERK pathways. 5) Clathrin-coated internalized vesicles is de-coated, and EGF is disassociated from the active EGFR. 6) The de-coated vesicles are fused with other intra-cellular vesicles. 7) When fused with lysosomes, EGFR is degraded. 8) When fused with vesicles from Golgi, EGFR can be recycled back to cytoplasma membrane. The signaling transduction mediated by different membrane units or sub-cellular components is also found in other receptor tyrosine kinases such as IFGR, HGFR and VEGFR. EGCG has been reported to inhibit this signaling pathway by interfering with the binding of EGF to EGFR, inhibiting EGFR kinase activity, altering lipid organization in the plasma membrane (lipid raft), and inducting EGFR internalization without activation as discussed in the text.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Yang CS, Wang H, Li GX, Yang Z, Guan F, Jin H. Cancer prevention by tea: Evidence from laboratory studies. Pharmacol Res. 2011;64:113–22. - PubMed
    1. Yang CS, Wang X, Lu G, Picinich SC. Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer. 2009;9:429–39. - PMC - PubMed
    1. Higdon JV, Frei B. Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Crit Rev Food Sci Nutr. 2003;43:89–143. - PubMed
    1. Crespy V, Williamson G. A review of the health effects of green tea catechins in in vivo animal models. J Nutr. 2004;134:3431S–3440S. - PubMed
    1. Sang S, Lambert JD, Ho CT, Yang CS. The chemistry and biotransformation of tea constituents. Pharmacological research : the official journal of the Italian Pharmacological Society. 2011;64:87–99. - PubMed

LinkOut - more resources

-