Abstract
4245
Background: Catechin is the key component of green tea, which has antibacterial, hypocholesterolemic, antioxidant, and anti-inflammatory activities. Among the several derivatives of catechin, (-)-epigallocatechin gallate (EGCG) is known to have the strongest biological activity, and is, in recent years, focused due to its anti-cancer properties. EGCG suppresses carcinogenesis, tumor growth, cancer metastasis, and tumor angiogenesis. Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that can activate strong cellular immunity, and tumor-infiltrating DCs are known to play an important role in the induction of anti-cancer immunity. At present, however, little is known on the effect of catechins on the immune system. OBJECTIVE: We aimed to investigate the effect of EGCG on human monocyte-derived DC (MoDC). METHOD: MoDCs were generated in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 and treated with different concentrations of EGCG. The induction of apoptosis was determined by annexinV-PI staining and the TUNEL assay. The activation of caspase-3, -8, and -9 was investigated by flow-cytometry. The changes in the surface expression of DC were also analyzed by flow-cytometry. RESULT: EGCG induced apoptosis of DCs in a dose-dependent manner, and the three key caspase molecules, caspase-3, -8, and -9, were activated by EGCG treatment. The expression of CD86, CD83, CD40, and MHC class II, which are molecules essential for antigen presentation, was down-regulated by EGCG. CONCLUSION: EGCG induces immunosuppressive alterations on human DC, both by induction of apoptosis and suppression of cell surface molecules. Although EGCG is a promising anti-tumor agent, by its direct effect on cancer cells, caution is necessary when using it for cancer treatment, since it may inhibit the function of tumor-infiltrating DCs, consequently inhibiting cellular immunity and antitumor reaction.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]
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