Abstract. Background Fucoidan is a complex sulfated polysaccharide consisting of sulfated fucose residues and found mostly in brown marine algae, echinoderms (1) and seagrasses (2). Fucoidans exhibit numerous biological activities found both in in vitro and in vivo experiments. Fucoidan extracts have been found to ameliorate acute colitis (3), have anticancer activity (4) mediate via natural killer (NK) cells (5) and affect inflammation, vascular physiology, as well as oxidative stress (6, 7). Some effects differ based on the type of extract, as documented by the differential effects of high and low molecular weight fucoidans on the severity of arthritis in mice. The low molecular weight samples reduced arthritis via suppression of Th1-mediated immunity, whereas high molecular weight samples enhanced the inflammatory activation of macrophages (8). Subsequent experiments revealed that high molecular weight fucoidans stimulated spleen cells, whereas low molecular weight samples had little activity or were toxic (9). The reasons for these differences are still unknown. Using a fish model, however, dietary fucoidan was found to influence blood chemistry and constituents, antioxidation and innate immunity (10). In human models, fucoidan delayed apoptosis and induced proinflammatory cytokines, probably via activation of the PI3K/AKT pathway (11). As fucoidan can function as an adjuvant and stimulate antibody response (12), it has been used to improve vaccine efficacy (13).Cancer development is the most studied effect of fucoidan. The mechanisms are still unknown. However, fucoidan can directly induce cytotoxicity and apoptosis of cancer cells (14) probably explained by an additional study suggesting implication of macrophages and blood leukocytes in relation to fucoidan (15).In our study, we not only directly compared the biological activities of individual fucoidan samples, but also compared purified samples with commercially available component mixtures. Thus, our study answers the question not only whether fucoidans influence immune reactions, but also if the popular idea of combining biologically active molecules together improves their effectiveness.
Materials and MethodsMaterials. Individual samples were purchased from the manufacturers or distributors as shown in Table I. RPMI 1640 medium, sodium citrate, 4-(2-hydroxyethyl)-1-piperazine-ethanol-sulfonic acid (HEPES), antibiotics, Wright stain, Freund's adjuvant, ovalbumin, Concanavalin A (Con A) and lipopolysaccharide (LPS) were purchased from Sigma (St. Louis, MO, USA). Fetal calf serum (FCS) was from Hyclone Laboratories (Logan, UT, USA).Cells. J774A.1 mouse macrophages and YAC cells were obtained from the ATCC (Manassas, VA, USA). The BALB/c mouse-derived mammary tumor cell line Ptac64 was generously provided by Dr. Wei-Zen Wei of the Michigan Cancer Foundation, Wayne State University, Detroit, MI, USA. The cell lines were maintained in RPMI 1640 medium containing HEPES buffer supplemented with 10% heat-inactivated FCS, 100 U/ml penicillin and 100 μg/ml stre...