title: Anti-tumor activity of fucoidan is mediated by nitric oxide released             from macrophages.
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.
authors.affiliation: Department of Microbiology and Oncology, Graduate School of Medicine,                     University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Takeda
authors.forename: Koh
authors.initials: K
authors.lastname: Tomimori
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Kimura
authors.forename: Chie
authors.initials: C
authors.lastname: Ishikawa
authors.forename: Tamara K
authors.initials: TK
authors.lastname: Nowling
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D011134:Polysaccharides / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D012510:Sarcoma 180 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D011134:Polysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; C007789:fucoidan; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse