Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 18, 2016; 8(29): 1222-1233
Published online Oct 18, 2016. doi: 10.4254/wjh.v8.i29.1222
Lycopene modulates cellular proliferation, glycolysis and hepatic ultrastructure during hepatocellular carcinoma
Prachi Gupta, Nisha Bhatia, Mohinder Pal Bansal, Ashwani Koul
Prachi Gupta, Nisha Bhatia, Mohinder Pal Bansal, Ashwani Koul, Department of Biophysics, Basic Medical Sciences Block II, Panjab University, Chandigarh 160014, India
Author contributions: All authors contributed to the manuscript.
Supported by University Grant Commission, New Delhi, No. 2060930310.
Institutional review board statement: The study was reviewed and approved by the Institutional Animal Ethics Committee (IAEC) of Panjab University, Chandigarh (India) and conducted according to the Indian National Science Academy guidelines for the use and care of experimental animals (IAEC/284-295 at Sr. No. 48).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Panjab University, Chandigarh, India [IACUC protocol number: (IAEC/284-295 at Sr. No. 48)].
Conflict-of-interest statement: The authors declare that there are no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ashwani Koul, Professor, Department of Biophysics, Basic Medical Sciences Block II, Panjab University, South Campus, Sec-25, Chandigarh 160014, India. drashwanikoul@yahoo.co.in
Telephone: +91-172-2534119
Received: May 4, 2016
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
Abstract
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 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).

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 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.

CONCLUSION

This study demonstrates that dietary supplementation with LycT has a multidimensional role in preventing HCC development.

Keywords: Hepatocellular carcinoma; Ultrastructure; Hypoxia; Cell proliferation; Lycopene; Glycolysis

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.