Lycopene enriched tomato extract exerts modulatory effects on hypoxia, angiogenesis and metastasis during N-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in mice

Abstract

The onset and progression of hepatocellular carcinoma (HCC) is associated with several molecular and physiological changes in the tumor microenvironment. This provides a rationale for studying these changes throughout hepatic carcinogenesis and their possible modulation by putative anti-cancer agents. The present study was designed to look into the effects of lycopene enriched tomato extract (LycT) on markers linked with hypoxia, angiogenesis and metastasis at advanced stages of N-nitrosodiethylamine (NDEA) induced HCC in mice. Female balb/c mice were divided into four groups: Control, NDEA, LycT and LycT+NDEA. LycT was able to inhibit tumor formation and retard the development of histoarchitectural alterations which was consonance with the serum levels of alpha-feto protein. HCC development was associated with aggravated expression of markers linked to hypoxia (HIF), angiogenesis (VEGF, CD 31) and metastasis (MMP-2, MMP-9). LycT mediated inhibition in tumorigenesis was accompanied by decrease in expression of these markers. ^99mTc-mebrofenin assay revealed diminished hepatic function in NDEA group which improved with LycT administration. These observations at late stages of HCC and those of the early stages reported previously, convincingly demonstrate that LycT effectively mitigated hepatic cancer possibly by modulating hypoxia, angiogenesis and metastasis.