Trapping of methylglyoxal by curcumin in cell-free systems and in human umbilical vein endothelial cells.

Curcumin, the most active compound of curcuminoids, has been shown to inhibit formation of advanced glycation end products (AGEs) in streptozotocin-induced diabetic rats. However, little is known on whether curcumin may trap methylglyoxal (MGO), a major reactive dicarbonyl compound, to inhibit AGE formation. We found that one molecule of curcumin effectively trapped one molecule of MGO at a 1:3 ratio at 24 h of incubation under physiological conditions (pH 7.4, 37 °C). Curcumin decreased N(ε)-(carboxymethyl)lysine (CML) expression in human umbilical vein endothelial cells. We further used two curcumin analogues, dimethoxycurcumin (DIMC) and ferulic acid, to investigate the possible MGO-trapping mechanism of curcumin. Results reveal that DIMC, but not ferulic acid, exhibited MGO-trapping capacity, indicating curcumin traps MGO at the electron-dense carbon atom (C10) between the two keto carbon groups. Thus, curcumin may prevent MGO-induced endothelial dysfunction by directly trapping MGO.

Antimetastatic effects and mechanisms of apo-8'-lycopenal, an enzymatic metabolite of lycopene, against human hepatocarcinoma SK-Hep-1 cells.

Lycopene is primarily metabolized by carotenoid monoxygenase II into apo-8'- and apo-12'-lycopenal in the rat liver. Although lycopene possesses antimetastatic activity in a highly invasive hepatoma SK-Hep-1 cell line, little is known whether its metabolites have a similar effect. In this study, we investigated the antimetastatic effects of apo-8'-lycopenal (1-10 µM) in comparison with lycopene (10 µM) in SK-Hep-1 cells. We found that both apo-8'-lycopenal and lycopene inhibited the invasion and migration of SK-Hep-1 cells, and the effect of apo-8'-lycopenal was stronger than that of lycopene at the same concentration (10 µM). Mechanistically, apo-8'-lycopenal: 1) decreased the activities and protein expression of metalloproteinase-2 (MMP-2) and -9; 2) increased the protein expression of nm23-H1 and the tissue inhibitor of MMP (TIMP)-1 and -2; 3) suppressed protein expression of Rho small GTPases; and 4) inhibited focal adhesion kinase-mediated signaling pathway, such as ERK/p38 and PI3K-Akt axis. Overall, these results demonstrate that apo-8'-lycopenal possesses antimetastatic activity in SK-Hep-1 cells and that this effect is stronger than that of lycopene, suggesting that the antimetastatic effect may be attributed, at least in part, to its metabolites such as apo-8'-lycopenal.