Sphingoid bases from sea cucumber induce apoptosis in human hepatoma HepG2 cells through p-AKT and DR5

Biofunctional marine compounds have recently received substantial attentionfor their nutraceutical characteristics. In this study, we investigated the apoptosis-inducingeffects of sphingoid bases prepared from sea cucumber using human hepatoma HepG2cells. Apoptotic effects were determined by cell viability assay, DNA fragmentationassay, caspase-3 and caspase-8 activities. The expression levels of apoptosis-inducingdeath receptor-5 (DR5) and p-AKT were assayed by western blot analysis, and mRNAexpression of bax, GADD45 and PPARγ was assayed by quantitative RT-PCR analysis.Sphingoid bases from sea cucumber markedly reduced the cell viability of HepG2cells. DNA fragmentation indicative of apoptosis was observed in a dose-dependentmanner. The expression levels of the apoptosis inducer protein Bax were increasedby the sphingoid bases from sea cucumber. GADD45, which plays an important rolein apoptosis-inducing pathways, was markedly upregulated by sphingoid bases fromsea cucumber. Upregulation of PPARγ mRNA was also observed during apoptosis inducedby the sphingoid bases. The expression levels of DR5 and p-AKT proteins were increasedand decreased, respectively, as a result of the effects of sphingoid bases fromsea cucumber. The results indicate that sphingoid bases from sea cucumber induceapoptosis in HepG2 cells through upregulation of DR5, Bax, GADD45 and PPARγ anddownregulation of p-AKT. Our results show for the first time the functional propertiesof marine sphingoid bases as inducers of apoptosis in HepG2 cells.