dieckol and Cell-Transformation--Neoplastic

Dieckol (DEK) is a major polyphenol of marine brown seaweed Ecklonia cava which is a potential candidate for cancer therapy. However, the underlying mechanism of DEK as an anticancer drug remains to be elucidated. In this study, we evaluated the molecular mechanisms involved in the chemopreventive efficacy of DEK in N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis rats by analyzing markers of xenobiotic-metabolizing enzymes (XMEs), apoptosis, invasion, and angiogenesis. Rats administered NDEA developed hepatocarcinogenesis that displayed apoptosis avoidance coupled to upregulation of pro-inflammatory, invasion, and angiogenesis markers. Treatment of DEK effectively suppressed the NDEA-initiated hepatocarcinogenesis by modulation of XMEs, inducing of apoptosis via the mitochondrial pathway as revealed by modulating the Bcl-2 family proteins, cytochrome C, caspases, and inhibiting invasion, and angiogenesis as evidenced by changes in the activities of MMPs (MMP2/9) and the expression of VEGF. In addition, DEK exerts its anticancer effects via inhibition of pro-inflammatory transcription factor NF-κB (nuclear factor κB) and COX2 in NDEA-induced hepatocarcinogenesis. Taken together, this study demonstrates that DEK modulates the expression of key molecules that regulate apoptosis, inflammation, invasion, and angiogenesis. These results strongly indicate that DEK from E. cava is an attractive candidate for chemoprevention.

Topics: Animals; Apoptosis; Benzofurans; Cell Proliferation; Cell Transformation, Neoplastic; Diethylnitrosamine; Liver Neoplasms; Male; Neoplasm Invasiveness; Neoplasm Proteins; Neovascularization, Pathologic; Rats; Rats, Wistar

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