Fucoidan from seaweed Fucus vesiculosus inhibits migration and invasion of human lung cancer cell via PI3K-Akt-mTOR pathways

• Published in: PloS one Vol. 7; no. 11; p. e50624
• Main Authors: Lee, Hyunkyoung, Kim, Jong-Shu, Kim, Euikyung
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30-11-2012; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Active Transport, Cell Nucleus - drug effects; AKT protein; Algae; Anticancer properties; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Biology; Breast cancer; Cancer; Cancer metastasis; Cancer treatment; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Diet; Dietary supplements; Extracellular signal-regulated kinase; Fucoidan; Fucus - chemistry; Fucus vesiculosus; Gelatinase A; Gene Expression Regulation, Neoplastic - drug effects; Growth factors; Humans; Invasiveness; Kinases; Lung cancer; Lung diseases; Lung Neoplasms - pathology; Matrix Metalloproteinase 2 - metabolism; Medicine; Melanoma; Metastases; Metastasis; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Natural products; Neoplasm Invasiveness; Neoplasm Metastasis; NF-kappa B - metabolism; NF-κB protein; Pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Polysaccharides; Polysaccharides - isolation & purification; Polysaccharides - pharmacology; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rapamycin; Rodents; Seaweeds; Signal transduction; Signal Transduction - drug effects; Signaling; Skin cancer; Studies; TOR protein; TOR Serine-Threonine Kinases - metabolism; Toxicology; Veterinary colleges; Veterinary medicine; Western blotting; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0050624

Recently there has been an increased interest in the pharmacologically active natural products associated with remedies of various kinds of diseases, including cancer. Fucoidan is a polysaccharide derived from brown seaweeds and has long been used as an ingredient in some dietary supplement products. Although fucoidan has been known to have anti-cancer activity, the anti-metastatic effects and its detailed mechanism of actions have been poorly understood. Therefore, the aims of this study were to demonstrate the anti-metastatic functions of fucoidan and its mechanism of action using A549, a highly metastatic human lung cancer cell line.
Fucoidan inhibits the growth of A549 cells at the concentration of 400 µg/ml. Fucoidan treatment of non-toxic dose (0-200 µg/ml) exhibits a concentration-dependent inhibitory effect on the invasion and migration of the cancer cell via decreasing its MMP-2 activity. To know the mechanism of these inhibitory effects, Western blotting was performed. Fucoidan treatment down-regulates extracellular signal-related kinase 1 and 2 (ERK1/2) and phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (PI3K-Akt-mTOR) pathways. Furthermore, fucoidan decreases the cytosolic and nuclear levels of Nuclear Factor-kappa B (p65).
The present study suggests that fucoidan exhibits anti-metastatic effect on A549 lung cancer cells via the down-regulation of ERK1/2 and Akt-mTOR as well as NF-kB signaling pathways. Hence, fucoidan can be considered as a potential therapeutic reagent against the metastasis of invasive human lung cancer cells.