title: Chemopreventive and hepatoprotective effects of Epigallocatechin-gallate against hepatocellular carcinoma: role of heparan sulfate proteoglycans pathway.
abstract: OBJECTIVE
  Epigallocatechin-gallate (EGCG) claims a plethora of health benefits including protection against neoplastic diseases. Meanwhile, heparan-sulfate proteoglycans (HSPGs) have defensive role against tumour cell invasion. Therefore, the chemopreventive and hepatoprotective effects of EGCG were studied in hepatocellular carcinoma (HCC) in vivo and in vitro and compared with strong water soluble antioxidant, sodium ascorbate.
  
  
  METHODS
  HCC was induced in SD rats by thioacetamide (200 mg/Kg). Some rats were treated with EGCG (20 mg/Kg) or sodium ascorbate (100 mg/Kg). Liver impairment was assessed by measuring serum α-fetoprotein and investigating liver sections stained with H/E. Hepatic HSPGs, syndecan-1 and matrix metalloproteinase-9 (MMP-9) were measured by ELISA. Gene expression of fibroblast growth factor (FGF)-2 was measured. Cell death was assessed by caspase-3 activity. In addition, all markers were measured in human hepatocellular carcinoma cell line (HepG2).
  
  
  RESULTS
  EGCG increased the animal survival and decreased both α-fetoprotein and HepG2 viability. In addition, EGCG ameliorated fibrosis and massive hepatic tissue breakdown. EGCG restored HSPGs and reduced expression of MMP-9, syndecan-1 and FGF-2 in-vivo and in-vitro. Sodium ascorbate showed significantly lower results than EGCG.
  
  
  CONCLUSIONS
  Besides antioxidant activity, other mechanisms are involved in the chemopreventive and hepatoprotective effects of EGCG including restoration of HSPGs receptors and inhibition of vascular invasion.
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Darweish
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abbas
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ebrahim
authors.forename: Mohammed M H
authors.initials: MM
authors.lastname: Al-Gayyar
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use; D028241:Camellia sinensis / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015870:Gene Expression; D056945:Hep G2 Cells; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D053668:Syndecan-1 / Q000378:metabolism; D013853:Thioacetamide; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D019812:Heparan Sulfate Proteoglycans; D010936:Plant Extracts; D053668:Syndecan-1; D000509:alpha-Fetoproteins; D013853:Thioacetamide; D016222:Fibroblast Growth Factor 2; D002392:Catechin; C045651:epigallocatechin gallate; D020780:Matrix Metalloproteinase 9; D001205:Ascorbic Acid
keywords: caspase-3; epigallocatechin-gallate; fibroblast growth factor; heparan sulfate proteoglycans; syndecan-1