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

• Published in: International journal of oncology Vol. 40; no. 1; pp. 251 - 260
• Main Authors: TAKEDA, Kaori, TOMIMORI, Koh, KIMURA, Ryuichiro, ISHIKAWA, Chie, NOWLING, Tamara K, MORI, Naoki
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01.01.2012
• Subjects: Animals; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Cell Cycle - drug effects; Cell Line, Tumor; Macrophages - drug effects; Macrophages - metabolism; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; NF-kappa B - metabolism; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - biosynthesis; Nitric Oxide Synthase Type II - genetics; Polysaccharides - pharmacology; Promoter Regions, Genetic; Random Allocation; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Sarcoma 180 - drug therapy; Sarcoma 180 - metabolism; Sarcoma 180 - pathology; Signal Transduction - drug effects; Tumors; Sarcoma; Enzyme; Malignant tumor; Fucoidan; Biological activity; Nitric-oxide synthase; inducible nitric oxide synthase; nuclear factor-κB; Cancerology; Nitric oxide; Oxidoreductases; Transcription factor NFκB; Cancer; Macrophage
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2011.1168

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.