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

Nutr Cancer. 2012;64(2):274-85. doi: 10.1080/01635581.2012.643273. Epub 2012 Jan 2.


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.

Publication types

  • Comparative Study

MeSH terms

  • Carcinoma, Hepatocellular
  • Carotenoids / administration & dosage
  • Carotenoids / metabolism*
  • Carotenoids / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Fatty Acids, Unsaturated / administration & dosage
  • Fatty Acids, Unsaturated / metabolism
  • Fatty Acids, Unsaturated / pharmacology*
  • Gene Expression / drug effects
  • Humans
  • Liver Neoplasms
  • Lycopene
  • Neoplasm Invasiveness / prevention & control
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / prevention & control*


  • Fatty Acids, Unsaturated
  • apo-8'-lycopenal
  • Carotenoids
  • Lycopene