| Tea polyphenols and curcuminoids have been reported to be potential cancer chemopreventive agents. Since modulation of arachidonic acid metabolism has been demonstrated to be an important target for cancer chemoprevention, the effects of the constituents on arachidonic acid metabolism in the gastrointestinal tract were investigated.; (−)-Epigallocatechin-3-gallate (EGCG), (−)-epigallocatechin (EGC), and (−)-epicatechin-3-gallate (ECG) and theaflavins (TFs) from green and black tea generally inhibited lipoxygenase (LOX)- and cyclooxygenase (COX)-dependent activity in normal colon mucosa. EGCG, ECG and TFs (50 μM) inhibited cytosolic phospholipase A2 (cPLA2) activity by 10–45%. Among curcuminoids, tetrahydrocurcumin (THC) (50 μM) inhibited cPLA2 activity by 36%. Tea polyphenols and curcuminoids showed stronger inhibitory action against arachidonic acid release in intact cells. At 510 μM, EGCG, ECG and curcumin inhibited the spontaneous and stimulator (A23187 and deoxycholic acid)- induced arachidonic acid release by over 50% in both KYSE esophageal and HT-29 colon cancer cells. The mechanisms involved in the inhibition by EGCG and curcumin may include inhibition of induction, up-regulation and/or translocation of cPLA2 as well as inhibition of translocation of 5-LOX. Green tea administration also significantly decreased leukotriene B4 level in azoxymethane-treated mouse colons.; The stability, uptake, biotransformation, and efflux of [3H]EGCG in HT-29 colon cancer cells were investigated. EGCG was unstable in culture media. The major oxidative products were EGCG dimers including theasinensin, which mainly binds to the cell surface. The uptake of EGCG was concentration-dependent, suggesting a passive diffusion process. Multi-drug resistant protein (MRP) inhibitors significantly increased the accumulation of [3H]EGCG in cells, suggesting an efflux of EGCG or its metabolites. EGCG metabolites including EGCG 3″-glucuronide and 4″-methyl EGCG were accumulated in the presence of indomethacin or probenecid, suggesting that the metabolites are substrates for MRP. This study established that the stability and uptake of EGCG by cell under culturing condition and provide a foundation to understand the biological actions of tea catechins.; The present study indicates that tea polyphenols and curcuminoids can modulate arachidonic acid metabolism in the gastrointestinal tract, and this action may be a possible mechanism in the prevention of many types of cancer, especially cancers of the digestive tract. |
