AIM To investigate the effect of lycopene extracted from tomatoes(LycT) on ultrastructure, glycolytic enzymes, cell proliferation markers and hypoxia during N-Nitrosodiethylamine(NDEA)-induced hepatocarcinogenesis. METHODS Female BALB/c mice were randomly divided into four groups: The Control, NDEA(200 mg NDEA/kg b.w. given i.p.), LycT(5 mg/kg b.w. given orally on alternate days) and Lyc T + NDEA group. The m RNA and protein expression of various cell proliferation markers(PCNA, Cyclin D1, and p21) were assessed by reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay, respectively. The ultrastructure of hepatic tissue was analyzed using scanning and transmission electron microscopy. The enzymatic activity of glycolytic enzymes was estimated using standardized protocols, while glucose-6-phosphate dehydrogenase activity level was estimated using a kit obtained from Reckon Diagnostic P. Ltd.(India). RESULTS Uncontrolled proliferation in the liver of NDEA(P ≤ 0.001) mice was evident from the high expression of cell-proliferation associated genes(PCNA, Cyclin D1, and p21) when compared to control and Lyc T mice. In addition, enhanced activities of hexokinase, phosphoglucoisomerase, aldolase, glucose-6-phosphatedehydrogenase and hypoxia-inducible factor-1α were observed in NDEA mice as compared to control(P ≤ 0.001) and Lyc T(P ≤ 0.001) mice. The alterations in hepatic ultrastructure observed in the NDEA group correlated with the changes in the above parameters. Lyc T pre-treatment in NDEA-challenged mice ameliorated the investigated pathways disrupted by NDEA treatment. Moreover, hepatic electron micrographs from the Lyc T + NDEA group showed increased macrophages, apoptotic bodies and well-differentiated hepatocellular carcinoma(HCC) in comparison to undifferentiated HCC as observed in the NDEA treated group. CONCLUSION This study demonstrates that dietary supplementation with Lyc T has a multidimensional role in preventing HCC development.
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