Anti-tumor activity of fucoidan is mediated by nitric oxide released from macrophages

Abstract

Abstract. Fucoidan, a sulfated polysaccharide, has significant cytotoxic activity against tumor cells; however, the mechanism(s) of this action remains poorly understood. The present study was designed to determine the in vitro and in vivo effects of fucoidan and their molecular mechanisms. Fucoidan from Cladosiphon okamuranus Tokida cultivated in Okinawa, Japan, delayed tumor growth in Sarcoma 180 (S-180)-bearing mice. However, it failed to inhibit S-180 cell growth in vitro. Activated macrophages are known to have anti-tumor effects. Murine RAW264.7 macrophages stimulated with fucoidan exerted cytotoxicity towards S-180 cells in vitro. This cytotoxicity was associated with nitric oxide (NO) production. Both cytocidal effect and NO production were significantly inhibited by L-NAME, an inhibitor of NO synthase (NOS). Furthermore, activation of nuclear factor-κB was a key step in the transcriptional activation of the inducible NOS gene. Taken together, our results indicate that the anti-tumor activity of fucoidan on S-180 cells is mediated through increased NO production by fucoidan-stimulated macrophages via nuclear factor-κB-dependent signaling pathway.

Fucoidan Can Function as an Adjuvant In Vivo to Enhance Dendritic Cell Maturation and Function and Promote Antigen-Specific T Cell Immune Responses

“…These data suggest that fucoidan may have the ability to enhance not only direct presentation of OVA by CD8α − cDCs but also cross-presentation of OVA by CD8α + cDCs. Since fucoidan can induce activation of macrophages [28] and other DC populations, such as langerhans cells (LCs), that are also able to cross-prime CTLs [29], [30], we are currently investigating whether fucoidan can induce CTL responses in mice that are depleted of macrophage and LCs.…”

Phycochemical Constituents and Biological Activities of Fucus spp.

“…Additional in vivo studies carried out in different models of colon, hepatocellular, sarcoma and leukemia cancer cells have also described positive effects for oral ingestion of fucoidans, although these were not from Fucus spp. origin [119,120,121]. …”

Fucoidan as a Marine Anticancer Agent in Preclinical Development

“…Fucoidan was found to prevent diethylnitrosamine-induced hepatocarcinogenesis by inhibiting metabolic activation of the carcinogen [30]. Takeda et al found that oral administration of fucoidan effectively inhibited growth of implanted Sarcoma-180 cells in xenograft mouse models [31]. Fucoidan likely mediated nitric oxide (NO) release by stimulated macrophages in the tumor microenvironment, thus causing apoptosis.…”

“…Furthermore, supernatants from fucoidan-stimulated macrophages were found to cause apoptosis of Sarcoma-180 cells. This effect was negated by the addition of a NO synthase inhibitor, N G -nitro- l -arginine methyl ester ( l -NAME) [31]. Xue et al demonstrated that β-catenin expression in tumor lesions was decreased significantly by fucoidan treatment of tumor-bearing mice [36].…”