Published online Oct 18, 2016. doi: 10.4254/wjh.v8.i29.1222
Peer-review started: May 5, 2016
First decision: June 6, 2016
Revised: June 20, 2016
Accepted: July 20, 2016
Article in press: July 22, 2016
Published online: October 18, 2016
Processing time: 162 Days and 22.4 Hours
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.
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 LycT + NDEA group. The mRNA 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).
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 LycT mice. In addition, enhanced activities of hexokinase, phosphoglucoisomerase, aldolase, glucose-6-phosphate dehydrogenase and hypoxia-inducible factor-1α were observed in NDEA mice as compared to control (P ≤ 0.001) and LycT (P ≤ 0.001) mice. The alterations in hepatic ultrastructure observed in the NDEA group correlated with the changes in the above parameters. LycT pre-treatment in NDEA-challenged mice ameliorated the investigated pathways disrupted by NDEA treatment. Moreover, hepatic electron micrographs from the LycT + 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.
This study demonstrates that dietary supplementation with LycT has a multidimensional role in preventing HCC development.
Core tip: The present study was designed to evaluate the chemopreventive role of lycopene extracted from tomatoes (LycT) against N-Nitrosodiethylamine-induced hepatocellular carcinoma (HCC). The findings suggested the mechanism underlying LycT-mediated chemoprevention of HCC.