dieckol and Carcinoma--Hepatocellular

Dieckol (DEK) is a naturally occuring phlorotannins found in marine brown algae Ecklonia cava which is attributed with various pharmacological properties. This study was aimed to investigate the protective role of DEK on N-Nitrosdiethylamine (NDEA) induced rat hepatocarcinogenesis. In this investigation 0.01% NDEA in drinking water for 15 weeks to induce hepatocellular carcinoma (HCC). DEK was administered orally (10, 20 and 40mg/kg body weight) for 15 weeks with 0.01% NDEA through drinking water. Hepatocarcinogesis was measured by the increased activities of serum liver marker enzymes namely aspartate trasaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), α-fetoprotein (AFP) and total bilirubin along with increased elevation of cytochrome p450, lipid peroxidation markers, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP), protein carbonyl content (PCC) and conjugated dienes (CD). The effect of NDEA was indicated by significant decreased activities of enzymatic antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR) and non-enzymatic antioxidants like reduced glutathione, vitamin C and vitamin E. The oral administration of DEK at a dose of 40mg/kg body weight significantly reversed the activities of hepatic marker enzymes, dercreased lipid peroxidative markers, increased antioxidant cascade and decreased NDEA concentration in liver. DEK at a dose of 40mg/kg body weight was highly effective when compared to other two doses (10 and 20mg/kg body weight). All these changes were accompanied by histopathological observations in liver. The obtained results clearly demonstrated that DEK prevents lipid peroxidation, hepatic cell damage and promote the enzymatic and non-enzymatic antioxidant defense system in NDEA-induced hepatocarcinogenesis which might be due to activities like scavenging of oxy radicals by Dieckol.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Benzofurans; Biomarkers; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Diethylnitrosamine; Lipid Peroxidation; Liver; Liver Function Tests; Liver Neoplasms, Experimental; Male; Oxidative Stress; Protein Carbonylation; Rats, Wistar

Phlorotannins have been reported to demonstrate several biological properties, including antioxidant activity, and activities useful in the treatment of diabetic complications and in chemoprevention of several vascular diseases. In this study, we focused on the apoptosis induced by dieckol, a marine algal phlorotannin isolated from Ecklonia stolonifera, on human hepatocellular carcinoma (HCC) Hep3B cells. Dieckol reduced the numbers of viable cells and increased the numbers of apoptotic cells in a dose-dependent manner. Immunoblotting analysis revealed that dieckol increased the expression levels of cleaved caspases-3, 7, 8, and 9, and cleaved poly(ADP-ribose) polymerase. Dieckol increased the permeability of mitochondrial membranes and the release of cytochrome c from mitochondria into the cytosol with apoptosis-inducing factor. In addition, dieckol induced increased expression of truncated Bid and Bim. The results indicate that dieckol induces apoptosis via the activation of both death receptor and mitochondrial-dependent pathways in HCC Hep3B cells.

Topics: Antineoplastic Agents; Apoptosis; Apoptosis Regulatory Proteins; Bcl-2-Like Protein 11; Benzofurans; BH3 Interacting Domain Death Agonist Protein; Carcinoma, Hepatocellular; Caspases; Cell Line, Tumor; Cell Survival; Cytochromes c; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HEK293 Cells; Humans; Liver Neoplasms; Membrane Proteins; Mitochondrial Membranes; Permeability; Phaeophyceae; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins