Antimetastatic Effects and Mechanisms of Apo-8 %26apos;-Lycopenal, an Enzymatic Metabolite of Lycopene, Against Human Hepatocarcinoma SK-Hep-1 Cells

作者：Yang Chih Min; Hu Te Yu; Hu Miao Lin^*

来源：Nutrition and Cancer-An International Journal, 2012, 64(2): 274-285.

DOI：10.1080/01635581.2012.643273

Lycopene is primarily metabolized by carotenoid monoxygenase II into apo-8%26apos;- and apo-12%26apos;-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%26apos;-lycopenal (1-10 mu M) in comparison with lycopene (10 mu M) in SK-Hep-1 cells. We found that both apo-8%26apos;-lycopenal and lycopene inhibited the invasion and migration of SK-Hep-1 cells, and the effect of apo-8%26apos;-lycopenal was stronger than that of lycopene at the same concentration (10 mu M). Mechanistically, apo-8%26apos;-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%26apos;-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%26apos;-lycopenal.

• 出版日期2012-3