title: Lycopene Enriched Tomato Extract Inhibits Hypoxia, Angiogenesis, and Metastatic Markers in early Stage N-Nitrosodiethylamine Induced Hepatocellular Carcinoma.
abstract: Targeting altered pathways during initial stage of hepatocellular carcinoma (HCC) development is viewed as an effective and promising strategy to control this disease. Present study investigated the potential effect of lycopene-enriched tomato extract (LycT) on hypoxia-induced factor (HIF)-1α, HOX, VEGF, CD31, matrix metalloproteinase (MMP)-2, MMP-9, and alpha fetoprotein (AFP)expression during initial stages of N-nitrosodiethylamine (NDEA) induced HCC. Female Balb/c mice (8-10 wk) were assigned to 4 groups: control, NDEA (200 mg NDEA i.p./kg body weight, cumulative), LycT (5 mg lycopene orally/kg body weight; 3 times a week), and LycT + NDEA. LycT treatment began 2 wk before NDEA administration and continued until the end of the 10 wk study. The onset of HCC by NDEA was associated with significant alteration in serum biochemical markers [alanine transaminases (ALT), aspartate transaminases (AST), and alkaline phosphatases (ALP), lactate dehydrogenase (LDH), urea, A/G ratio, and bilirubin] and in liver histopathology. LycT treatment significantly reduced the levels of these markers. LycT treatment to NDEA mice also led to significant reduction in protein levels of AFP, HIF-1α, VEGF, CD31, MMP-2, and MMP-9 in comparison with NDEA group alone. These parameters are important biomarkers of hypoxia, angiogenesis, and metastasis, which reflect the advanced disease stage. The study provides evidence that prophylactic dietary supplementation with LycT may counteract HCC progression and/or protect against disease onset.
authors.affiliation: a Department of Biophysics , Basic Medical Sciences Block, Panjab University , Chandigarh , India.
authors.forename: Nisha
authors.initials: N
authors.lastname: Bhatia
authors.affiliation: a Department of Biophysics , Basic Medical Sciences Block, Panjab University , Chandigarh , India.
authors.forename: Prachi
authors.initials: P
authors.lastname: Gupta
authors.affiliation: a Department of Biophysics , Basic Medical Sciences Block, Panjab University , Chandigarh , India.|b Department of Nuclear Medicine , Post Graduate Institute of Medical Education and Research (PGIMER) , Chandigarh , India.
authors.forename: Baljinder
authors.initials: B
authors.lastname: Singh
authors.affiliation: a Department of Biophysics , Basic Medical Sciences Block, Panjab University , Chandigarh , India.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Koul
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D002338:Carotenoids / Q000008:administration & dosage*; D015687:Cell Hypoxia / Q000187:drug effects; D019587:Dietary Supplements; D004052:Diethylnitrosamine; D005260:Female; D005638:Fruit / Q000737:chemistry; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010936:Plant Extracts / Q000737:chemistry*
chemical_list: D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D010936:Plant Extracts; D002338:Carotenoids; D004052:Diethylnitrosamine; D000077276:Lycopene