Effect Of Fucoidan And Germacrone On Cancer Cell Lines And The Underlying Mechanisms

Fucoidan is one of the main bioactive components of polysaccharides. About4percent of the total dry weight of many types of brown seaweed consists of polysaccharides known as fucoidan. Fucoidan is a sulfated polysaccharide that possesses a complex structure. Chief components include sulfuric esterified L-fucose, trace elements of galactose, xylose and glucronic acid. The search for new drugs has raised interest in fucoidans.The current study was focused on the anti-tumor effects of fucoidan on human hepatoma cell line HepG2and the possible mechanisms. Fucoidan treatment resulted in cell cycle arrest and apoptosis of HepG2cells in a dose-dependent manner at concentrations of0,0.2,1,2,4and6mg/ml. The results of Flow cytometric analysis revealed that fucoidan induced G2/M arrest in the cell cycle progression. Hoechst33258and Annexin V/PI staining results showed that the apoptotic cell number was increased, which was associated with a dose-dependent up-regulation of Bax and down-regulation of Bcl-2and p-Stat3. In parallel, the up-regulation of p53and the increase in reactive oxygen species were also observed, which may play important roles in the inhibition of HepG2growth by fucoidan. At the meantime, Cyclin B1and CDK1were down-regulated after fucoidan treatment. Down regulation of p-Stat3by fucoidan resulted in apoptosis and an increase in ROS. We therefore conclude that fucoidan induces apoptosis through the down regulation of p-Stat3.The above results suggest that fucoidan may be used as a novel anti-cancer agent for hepatocarcinoma.Preliminary investigation on effects of fucoidan on neuroblastoma cells SH-SY5Y was also carried out. SH-SY5Y is a human derived cell line used in scientific research. Fucoidan at a low concentration increased the cell viability in dose-and time-dependent manners. Cell cycle phase analysis revealed that fucoindan at0.8mg/ml increased the cell percentage of S phase markedly compared with the control.In another study experiment, we preliminarily assayed the effect of germacrone, one of the major components of essential oils of R. curcuma, on the proliferation of Be17402cells and its action mechanism. MTT assay was used to test the effect of germacrone on proliferation of Be17402and L02cells. Apoptosis and ROS production of Be17402cell was detected by Flow cytometry. The protein expression of p53, Bax and Bcl-2were investigated by Western blot. Results showed that germacrone could inhibit the proliferation of Bel7402cells in the dose-dependent way, and germacrone promoted apoptosis and increased ROS generation in Be17402cells at the same time. The increasing protein expression of p53and Bax and decreasing protein expression of Bcl-2were also observed in Be17402cells. It is concluded that germacrone inhibits proliferation of Be17402cells through regulation of p53, Bax and Bcl-2and increase of ROS production.Results obtained in this study provided with useful reference for clarifying the molecular mechanism of anti-tumor effect and development of new anti-tumor drugs.