Lycopene supplementation inhibited high‐fat diet‐promoted hepatic tumorigenesis in both wild‐type and beta‐carotene‐9’,10’‐oxygenase knockout mice (123.1)

Obesity is associated with increased liver cancer risks, morbidity and mortality. A recent study (Ip et al ., 2013) showed that apo‐10’‐lycopenoic acid, a lycopene (LYC) metabolite generated by beta‐carotene‐9’,10’‐oxygenase (BCO2), inhibited carcinogen‐initiated, high‐fat diet (HFD)‐promoted liver inflammation and tumor development. This present investigation examined whether LYC can suppress HFD‐promoted hepatic inflammation and tumorigenesis in BCO2‐knockout (BCO2‐KO) and the respective wild‐type (WT; 129SvJ/SvEvTac) mice. Results showed that 24‐week LYC supplementation (100 mg/kg diet) had similar effects on suppressing HFD‐promoted liver tumor incidence (by 19% vs 20%), number (by 56% vs 55%) and volume (by 96% vs 95%) in WT and BCO2‐KO mice, respectively. LYC chemopreventative effects were associated with reduced pro‐inflammatory signaling (NF‐κB p65, STAT3 phosphorylation; IL‐6 protein), F4/80 gene expression and inflammatory foci (p=0.06) in the livers of WT but not BCO2‐KO mice. On the contrary, protective effects of LYC in BCO2‐KO mice were associated with reduced endoplasmic reticulum stress‐mediated unfolded protein response (IRE1α, PERK signaling pathways) that is linked to increased liver cancer risks. Taken together, this data indicated that LYC can prevent HFD‐promoted hepatic tumorigenesis in mice, but may involve differential mechanisms depending on BCO2 expression. Grant Funding Source : USDA/ARS grant 1950‐51000‐074S