title: Sphingoid bases from sea cucumber induce apoptosis in human hepatoma             HepG2 cells through p-AKT and DR5.
abstract: Biofunctional marine compounds have recently received substantial attention             for their nutraceutical characteristics. In this study, we investigated the apoptosis-inducing             effects of sphingoid bases prepared from sea cucumber using human hepatoma HepG2             cells. Apoptotic effects were determined by cell viability assay, DNA fragmentation             assay, caspase-3 and caspase-8 activities. The expression levels of apoptosis-inducing             death receptor-5 (DR5) and p-AKT were assayed by western blot analysis, and mRNA             expression of bax, GADD45 and PPARγ was assayed by quantitative RT-PCR analysis.             Sphingoid bases from sea cucumber markedly reduced the cell viability of HepG2             cells. DNA fragmentation indicative of apoptosis was observed in a dose-dependent             manner. The expression levels of the apoptosis inducer protein Bax were increased             by the sphingoid bases from sea cucumber. GADD45, which plays an important role             in apoptosis-inducing pathways, was markedly upregulated by sphingoid bases from             sea cucumber. Upregulation of PPARγ mRNA was also observed during apoptosis induced             by the sphingoid bases. The expression levels of DR5 and p-AKT proteins were increased             and decreased, respectively, as a result of the effects of sphingoid bases from             sea cucumber. The results indicate that sphingoid bases from sea cucumber induce             apoptosis in HepG2 cells through upregulation of DR5, Bax, GADD45 and PPARγ and             downregulation of p-AKT. Our results show for the first time the functional properties             of marine sphingoid bases as inducers of apoptosis in HepG2 cells.
authors.affiliation: Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. hossain5@cc.umanitoba.ca
authors.forename: Zakir
authors.initials: Z
authors.lastname: Hossain
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sugawara
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirata
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004354:Drug Screening Assays, Antitumor; D004983:Ethanolamines / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D012616:Sea Cucumbers / Q000737:chemistry*; D013110:Sphingosine / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics; D000097642:GADD45 Proteins
chemical_list: D000970:Antineoplastic Agents; D053148:Caspase 3; D053181:Caspase 8; D018797:Cell Cycle Proteins; D004983:Ethanolamines; D009687:Nuclear Proteins; D047494:PPAR delta; D051057:Proto-Oncogene Proteins c-akt; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D013110:Sphingosine; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C003337:sphingadienine; C505407:CASP3 protein, human; C505530:CASP8 protein, human