title: Chemopreventive and hepatoprotective roles of adiponectin (SULF2 inhibitor) in hepatocelluar carcinoma.
abstract: Sulfatase 2 (SULF2) is an extracellular enzyme that catalyzes the removal of 6-O-sulfate groups from the heparan sulfate (HS). As elevated SULF2 activity has been correlated with hepatocellular carcinoma (HCC), this study was conducted to evaluate the chemoprotective and the hepatoprotective roles of adiponectin, as a SULF2 inhibitor, against hepatocellular carcinoma both in vivo and in vitro. HCC was induced in rats using thioacetamide (200 mg/kg). Treated rats received adiponectin (5 μg/kg) once a week. Moreover, human hepatocellular carcinoma (HepG2) cell line was used as an in-vitro model. In both in-vivo and in-vitro models, adiponectin completely blocked HCC-induced SULF2 elevation. The antitumor activity of adiponectin was confirmed by 80% increased the survival rate, 73% reduction in the average number of nodules per nodule-bearing liver and 46% reduction in serum AFP. In addition, adiponectin ameliorated HCC-induced expression of tumor invasion markers, MMP9, syndecan-1 and FGF-2. Moreover, adiponectin attenuated HCC-induced elevation of nfκb and TNF-α levels. Moreover, treatment of HepG2 cell line with adiponectin showed dose-dependent reduction of HepG2 cell viability and elevation of cellular cytotoxicity. Besides, Adiponectin yielded the same results in HepG2 cells in a dose-dependent manner. Adiponectin achieved both hepatoprotective and chemoprotective effects against HCC through blocking of SULF2.
authors.forename: Mohammed M H
authors.identifier: http://orcid.org/0000-0003-4777-3919
authors.initials: MM
authors.lastname: Al-Gayyar
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abbas
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Hamdan
mesh_terms: D052242:Adiponectin / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015238:Sulfotransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D052242:Adiponectin; D000970:Antineoplastic Agents; C547680:Sulf2 protein, rat; D015238:Sulfotransferases