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.
Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.
Chih-Min
CM
Yang
Te-Yu
TY
Hu
Miao-Lin
ML
Hu
D006528:Carcinoma, Hepatocellular; D002338:Carotenoids / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms; D000077276:Lycopene; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000235:genetics / Q000517:prevention & control*
D005231:Fatty Acids, Unsaturated; C572536:apo-8'-lycopenal; D002338:Carotenoids; D000077276:Lycopene