Department of Pharmacology and Toxicology, College of Veterinary Medicine, Gyeongsang National University, Jinju, South Korea.
PLoS One. 2012;7(11):e50624. doi: 10.1371/journal.pone.0050624. Epub 2012 Nov 30.
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).
CONCLUSIONS/SIGNIFICANCE: 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.
近年来，人们对与各种疾病（包括癌症）治疗相关的具有药理活性的天然产物越来越感兴趣。褐藻糖胶是一种从褐藻中提取的多糖，长期以来一直被用作某些膳食补充产品的成分。尽管褐藻糖胶已被证实具有抗癌活性，但它的抗转移作用及其详细的作用机制仍知之甚少。因此，本研究旨在使用高转移性人肺癌 A549 细胞系证明褐藻糖胶的抗转移功能及其作用机制。
褐藻糖胶在 400μg/ml 的浓度下抑制 A549 细胞的生长。褐藻糖胶在无毒剂量（0-200μg/ml）下处理，通过降低其基质金属蛋白酶-2（MMP-2）活性，表现出浓度依赖性抑制癌细胞侵袭和迁移的作用。为了了解这些抑制作用的机制，进行了 Western blot 分析。褐藻糖胶处理下调细胞外信号调节激酶 1 和 2（ERK1/2）和磷酸肌醇 3-激酶（PI3K）-Akt-雷帕霉素靶蛋白（PI3K-Akt-mTOR）通路。此外，褐藻糖胶降低了核因子-κB（p65）的胞质和核水平。
结论/意义：本研究表明，褐藻糖胶通过下调 ERK1/2 和 Akt-mTOR 以及 NF-κB 信号通路，对 A549 肺癌细胞表现出抗转移作用。因此，褐藻糖胶可以被认为是一种潜在的治疗侵袭性人肺癌细胞转移的试剂。
