Journal
JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 66, Issue 7, Pages 1032-1045Publisher
WILEY
DOI: 10.1111/jphp.12229
Keywords
caspase-3; epigallocatechin-gallate; fibroblast growth factor; heparan sulfate proteoglycans; syndecan-1
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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 (200mg/Kg). Some rats were treated with EGCG (20mg/Kg) or sodium ascorbate (100mg/Kg). Liver impairment was assessed by measuring serum -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). Key findings EGCG increased the animal survival and decreased both -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.
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