(−)-Epigallocatechin Gallate and Polyphenon E Inhibit Growth and Activation of the Epidermal Growth Factor Receptor and Human Epidermal Growth Factor Receptor-2 Signaling Pathways in Human Colon Cancer Cells

Abstract

Purpose: (À)-Epigallocatechin gallate (EGCG) inhibits activation of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2) and multiple downstream signaling pathways in cancer cell lines. In this study we compared the cellular and molecular effects of EGCG with a well-standardized decaffeinated green tea catechin mixture Polyphenon E (Poly E) on human colon cancer cell lines. Experimental Design and Results: Both EGCG and Poly E preferentially inhibited growth of the Caco2, HCT116, HT29, SW480, and SW837 colon cancer cells when compared with the FHC normal human fetal colon cell line. The EGFR and HER2 proteins were overexpressed and constitutively activated in all of the colon cancer cell lines when compared with the FHC cell line. Treatment of HT29 cells with EGCG or Poly E caused an increase of cells in G 1 and induced apoptosis. Both EGCG and Poly E caused a decrease in the phosphorylated forms of EGFR and HER2 proteins, and subsequently caused a decrease in the phosphorylated forms of the extracellular signal-regulated kinase and Akt proteins. Similar effects of these compounds were seen when the cells were stimulated with transforming growth factor a. Reporter assays indicated that both EGCG and Poly E inhibited the transcriptional activity of the activator protein 1 (AP-1), c-fos, nuclear factor nB, and cyclin D1promoters.The combination of only 1 Mg/mL of epicatechin plus 10 Mg/mL of EGCG displayed synergistic effects on growth inhibition and induction of apoptosis. Furthermore, when treatment was prolonged for 96 hours, 1 Mg/mL of EGCG or Poly E was sufficient to inhibit growth, reduce activation of EGFR and HER2, and induce apoptosis. Conclusion: Our findings suggest that EGCG or Poly E may be useful in the chemoprevention and/or treatment of colon cancer. Poly E contains about 60% EGCG, yet pure EGCG and Poly E had similar potencies (expressed as Mg/mL). Poly E may be preferable because it is easier to prepare and this mixture of catechins may exert synergistic effects.

The growth inhibitory effect of actein on human breast cancer cells is associated with activation of stress response pathways

“…49 Since we found that relatively low concentrations of actein can cause synergistic inhibition of the proliferation of breast cancer cells when combined with chemotherapy agents, actein might enhance the efficacy of other agents with respect to breast cancer prevention and therapy. 48 …”

Ultraviolet Irradiation Can Induce Evasion of Colon Cancer Cells from Stimulation of Epidermal Growth Factor

“…2 family, which are frequently overexpressed in several types of human cancers, including cancers of the lung (1), head and neck (2), prostate (3), breast (4), pancreas (5), and colon (6), have been associated with abnormal growth of these tumors. It is well known that exposure of cells to EGF results in rapid autophosphorylation of EGFR molecules at the cell surface (7)(8)(9)(10), which upon activation lead to cell proliferation, motility, and enhanced survival (11).…”

Cancer Preventive Mechanismsof the Green Tea Polyphenol (-)-Epigallocatechin-3-gallate

“…Shimizu et al [30] have reported that EGCG (at 10-20 µg/mL) was shown to inhibit the activation of the EGFR, HER2, and multiple downstream signaling pathways in colon cancer cell lines. Tachibana et al [31] found that EGCG bound to a specific metastasis associated 67kDa laminin receptor that was expressed on a variety of tumor cells.…”