الفهرس 
Introduction & Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) pathogenesis involves the interplay of multiple signaling pathways. Notch and Hedgehog (Hh) are two major developmental pathways that act in concert to regulate adult cell repair. CK2 -serine-threonine kinase- down-regulation enhanced apoptotic activity and was proven beneficial for HCC patients. Quercetin is a bioactive flavonoid and has been shown to protect against HCC through its antioxidant activity. This study was carried out to elucidate the antineoplastic effect of quercetin through regulating both Notch and Hh pathways, apoptosis, cell proliferation and CK2 activity. Hepatocellular carcinoma was induced in male Sprague Dawley rats by thioacetamide. Quercetin was administered in both protective and curative doses. Parameters of liver function and oxidative stress were assessed. CK2, Notch and Hh pathways were evaluated using RT-PCR and ELISA. Apoptosis was investigated by detecting caspase-3, caspase-8 and p53. Proliferative and cell cycle markers as cyclin D1 and Ki-67 were detected immunohistochemically. Quercetin inhibited CK2 and downregulated mRNA and protein expression of Notch1 and Gli2. Quercetin also suppressed caspase-3 and p53 expression but not caspase-8. Proliferative and cell cycle markers cyclin D1 and Ki-67 were also downregulated. Markers of hepatic cellular integrity such as AST, ALT, ALP, GGT, albumin and bilirubin were significantly ameliorated. This was confirmed by histological examination. Quercetin also alleviated oxidative stress as shown by SOD, GSH, MDA and NO levels. We can conclude that in addition to its antioxidant power, quercetin blocked Notch, Hedgehog, the apoptotic and proliferative pathways and inhibited CK2 in HCC.