Tea has a component known as “EGCG”. EGCG has reportedly been found to inhibit cell growth and to induce apoptosis with human lung cancer cell lines and the Ha-ras gene transformed human bronchia epithelial 21BES cell line.

The targets for the chemopreventive and anti-cancer effects of EGCG have not been clearly elucidated. EGCG has multiple biological effects by acting on different targets directly or indirectly. EGCG has been reported to inhibit a number of enzymes and signal transduction pathways such as the following.

• Blocks EGF receptor and platelet derived growth factor : This can inhibit the growth factor induced activation of activator protein 1, a transcription factor critically involved in the action of various growth factors and cytokines. Additionally, EGCG it has been reported that EGCG inhibits adhesion kinase activity, indicating a negative interference of green tea with cell adhesion and cell movement process. 
• CDK inhibitor p21: EGCG has been reported to crease the expression of the CDK inhibitor p21 in human breast carcinoma cells. 
• AP-1: Exposure to UVB radiation is associated with human non-melanoma skin cancer and exposure induces AP-1 activation. EGCG inhibits UVB-induced in cultured human keratinocytes. 

In H-as-transformed JB6, the H-ras-activated AP-1 pathway is a major growth stimulant. In these cells, the AP-1 activation was inhibited by EGCG, EGC, theaflavin-3,3′-digallate and other polyphenols and the inhibition of the phosphorylation of  was inhibited. Because the ras genes are activated in many animal carcinogenesis models and in human cancers, inhibition of the phosphorylation of c-jun and Erk could be an important mechanism for the inhibition of cancer formation and growth.

•  EGCG has been reported to inhibit activation of the MAPKs,  in human epidermal keratinocytes after exposure to UV-B radiation and oxidative stress. For example, the phosphorylation of ERK1 and ERK2 in normal NIH-pATMras cells was reportedly not affected by EGCG wherase phosphoyrlation was significantly decreased in transformed cells. 

EGCG also reportedly inhibited UVB induced upregulation of these MAPK proteins in mouse skin. Increased AP-1 activity has been shown to be involved in the promotion and progression of various types of cancers. Thus inhibition of AP-1 activation may be a relevant molecular target for for EGCG. It is suggested that treatment of EGCG prevents UVB induced phosphorylation of MAPK by preventing UVB induced oxidative stess such as depletion of antioxidant enzymes and prevention of LPO and protein oxidation. Prevention of 

phosphorylation of MAPK proteins may thsu prevent the down stream events such as activation of AP-1 and NF-kB which would lead to the prevention of photocarcinogenic events in the skin.

macrophages: In murine peritoneal macrophages and the macrophage cell line (J774.1) EGCG inhibited LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), but not Jun N-terminal kinase (JNK), while it augmented LPS induced phosphorylation of p44/p42 extracellular signal-related kinase (ERK).

EGCG has been reported to inhibit Jun, a nuclear proto-oncogene which constitutes a part of the transcription factor AP-1 while at the same time having a minimal effect on cellular Jun content of normal cells.

Human Leukemia cell lines: EGCG has been reported to induce activation of both JNK and p38 in U937 and OCI-AML1a cell lines.

Mouse Skin: UVB irradiation of mouse skin induced phosphorylation of ERK1/2, JNK, and p38. Topic application of EGCG reportedly inhibited this inducement

• TNF?: Inibition of TNF? has also been proposed as a possible mechanisms for the cancer preventive activity of EGCG. 
• NF-?pathway: EGCG also has profound effects on the NF-?pathway which may also contribute to the anticarcinogenic effect of tea polyphenols . 

human leukemic cell line: (U937 cells) EGCG did not induce degradation of IkB-alpha, the essential upstream signalling even of NF-kB activation. 

• ornithine decarboxylase (ODC) has been closely linked with cellular proliferation and has been regarded as an oncogene. EGCG has been reported to cause a progressive decrease of ODC protein in transformed cells. 
• Phosphorylation by tyrosine kinase: Tyrosine kinase plays an important role in signal transduction and in malignant transformation processes. Increased tyrosien phosphorylation fo a 130 kD protein has been implicated in cell transformation by Src-family tyrosine kinases. EGCG has been reported to inhibit tyrosine phosphorylation while not affecting it in normal cells.

  PDGF and epidermal growth factor (EGF) result in activation of receptor tyrosine kinases, which then activate Ras, Raf, and MAPK phosphorylation that in turn activate transcription factors such as c-fos, c-jun, c-myc and other intermediate genes. EGCG has been shown to reduce the autophosphorylation level of EGF-R induced by EGF. In addition, EGCG blocked EGF binding to its receptor. 

  • Apoptosis: More apoptosis has been reportedly induced in transformed cells than in normal controls by EGCG. Interestingly a number of pathogens (e.g., C. pneumoniae) inhibit apoptosis (mitochondrial cytochrome c release and caspase 3 activation). Could EGCG counteract these effects too?
  • Free radicals: Reactive oxygen species (ROS) are low molecular mass compounds, including superoxide anion radical, hydrogen peroxide, singlet oxygen and hydroxyl radicals that are associated with normal cellular metabolism. Accumulating evidence suggests that ROS, produced by either endogenous or exogenous sources are critically involved in multiple stages of carcinogenesis. A number of polyphenolic compounds extracted form green tea leaves have been found to be good antioxidants against lipid peroxidation in phospholipid bilayers. 

  In brief, H2O2 production was added to LHC-9 medium either in the prsence or in the absence of cells and with or without catalase (30 units/mL). At different time points the amount of H2O2 in medium were analyzed using H2O2 the H2O2 assay kit (Molecular Probes, Eugene, OR). The presence of catalase delayed the EGCG induced onset of cell death, usggesting that H2O2 is in part involved in the EGCG induced apoptosis. 

  Treatment with EGCG activated components of the TGF? signaling pathway, including TGF?and TGF-?2 and TGF-?-stimulated protein TSC22, SMAD2, SMAD3, and SMAD6, and SMAD anchor for receptor activation (SARA) and some downstream targets including fibronectin, firbroniectin receptor, laminin, laminin receptor. Treating cells with ctalase abolished the activation of these genes. In contrast, decreased expression of a gene cluster of the BMP signaling pathway including its BMPR2, SMAD7 and some components of the MAPK pathway, FK506 binding protein 5, cullin5, were not blocked by catalase. BMPs belong to the t

  • Enzymes involved in DNA replication: Catechins has been shown to inhibit DNA replication in various leukemia cancer cell lines. (It has even been found to inhibit the activities of cloned HIV-1 RT), duck hepatitis B virus replications complexes reverse transcriptase, herpes simplex virus 1 DNA polymerase and cow thymus DNA polymerase alpha.