title: Modulatory efficacy of dieckol on xenobiotic-metabolizing enzymes, cell proliferation, apoptosis, invasion and angiogenesis during NDEA-induced rat hepatocarcinogenesis.
abstract: 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.
authors.affiliation: Centre of Advanced Study in Marine Biology, Faculty of Marine Sciences, Annamalai University, Parangipettai, Chidambaram, Tamil Nadu, 608 502, India. sentbiot@gmail.com.|Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Tamil Nadu, 608 002, India. sentbiot@gmail.com.
authors.forename: Velayutham
authors.initials: V
authors.lastname: Sadeeshkumar
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram, Tamil Nadu, 608 002, India.|Division of Neurology, Department of Medicine, University of Alberta, Edmonton, AB, T6G 2G3, Canada.
authors.forename: Arul
authors.initials: A
authors.lastname: Duraikannu
authors.affiliation: Centre of Advanced Study in Marine Biology, Faculty of Marine Sciences, Annamalai University, Parangipettai, Chidambaram, Tamil Nadu, 608 502, India.
authors.forename: Samuthrapandian
authors.initials: S
authors.lastname: Ravichandran
authors.affiliation: Department of Chemistry, Faculty of Science, Annamalai University, Chidambaram, Tamil Nadu, 608 002, India.
authors.forename: Paulrasu
authors.initials: P
authors.lastname: Kodisundaram
authors.affiliation: Centre of Advanced Study in Marine Biology, Faculty of Marine Sciences, Annamalai University, Parangipettai, Chidambaram, Tamil Nadu, 608 502, India.
authors.forename: Wilson Sylvester
authors.initials: WS
authors.lastname: Fredrick
authors.affiliation: Centre of Advanced Study in Marine Biology, Faculty of Marine Sciences, Annamalai University, Parangipettai, Chidambaram, Tamil Nadu, 608 502, India.
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Gobalakrishnan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001572:Benzofurans / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004052:Diethylnitrosamine / Q000633:toxicity*; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001572:Benzofurans; D009363:Neoplasm Proteins; C503840:dieckol; D004052:Diethylnitrosamine
keywords: Angiogenesis; Apoptosis; Dieckol; Hepatocarcinogenesis; Invasion