Enzyme-digested Fucoidan Extracts Derived from Seaweed Mozuku of Cladosiphon novae-caledoniae kylin Inhibit Invasion and Angiogenesis of Tumor Cells

Abstract

Fucoidan is a uniquely-structured sulfated polysaccharide found in the cell walls of several types of brown seaweed that has recently, especially as enzyme-digested fucoidan extract, attracted a lot attention due to its anti-tumor potential. In this study, we evaluated the effects of enzyme-digested fucoidan extracts prepared from seaweed Mozuku of Cladosiphon novae-caledoniae kylin on in vitro invasion and angiogenesis abilities of human tumor cells. First, we evaluated the effect of the fucoidan extracts on oxidative stress of tumor cells, and demonstrated that intracellular H(2)O(2) level and released H(2)O(2) from tumor cells were both greatly repressed upon the treatment with the fucoidan extracts, suggesting that fucoidan extracts ameliorate oxidative stress of tumor cells. Next, we tested for the effects of fucoidan extracts on invasion ability of human fibrosarcoma HT1080 cells, showing that fucoidan extracts significantly inhibit their invasion, possibly via suppressing matrix metalloproteinases (MMPs) MMP-2/9 activities. Further, we investigated the effects of the fucoidan extracts on angiogenesis of human uterine carcinoma HeLa cells, and found that fucoidan extracts suppressed expression and secretion of an angiogenesis factor vascular endothelial growth factor (VEGF), resulting in suppressed vascular tubules formation of tumor cells. The results taken together clarified that enzyme-digested fucoidan extracts from Cladosiphon novae-caledoniae kylin possess inhibitory effects on invasion and angiogenesis of tumor cells. These effects might, at least partially, be elicited by the antioxidative potential of enzyme digested fucoidan extracts.

Fucoidan induces Apoptosis in MDA-MB-231 Cells by Activating Caspase Cascade and Down-regulating XIAP

“…A number of genes that are associated with apoptotic cell death were tested in order to clarify the mechanism by which fucoidan treatment induces apoptosis in MDA-MB-231 cells. According to some previously conducted studies, caspases act as key players of fucoidan-induced apoptosis [20][21][22][23][24][25][26][27] . These findings have guided the researcher to propose a model in which fucoidan promotes apoptosis in MDA-MB-231 cells through increasing caspases activity.…”

“…Fucoidan, a class of fucose-enriched sulfated polysaccharides, is a naturally occurring polysaccharide compound in brown alga, such as Fucus vesiculosus, Cladosiphon okamuranus and Laminaria saccharina [1,2] . It has recently been reported that fucoidan possesses a wide variety of biological activities, including anticoagulant, antiviral, antiangiogenic, anticancer and immune-modulatory activities [3] . Studies in vitro have indicated that fucoidan exhibits protection effect against various cancers, including human lymphoma, promyelocytic leukemia, colon carcinoma, breast carcinoma, hepatoma and melanoma.…”

Catalyser-21TM, a mineral water derived from leaf soil, inhibits tumor cell invasion and angiogenesis

“…Thus, regulation of MMP-2 and MMP-9 activity remains a way of controlling cancer progression. A brown algal extract was shown to inhibit MMP activity and was proposed as a candidate antimetastatic agent as well as for use in other chronic disorders (Ye et al 2005;Kim 2006). It has been reported that a mixture of four herb extracts inhibits the invasive potential of hepatocellular carcinoma by inhibiting MMP activity (Ha et al 2004), and an approach to the development of an anticancer agent by inhibiting MMP activity has been demonstrated (Roomi et al 2006a, b, c).…”

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

“…Previous studies have shown that fucoidan has significant biological activities, such as anti-bacterial (2), anti-viral (3), anti-coagulant (4), anti-oxidant (5), anti-inflammatory (4,6) and immunomodulatory effects (2,7). Other studies also described anti-carcinogenic properties (8)(9)(10)(11)(12)(13)(14)(15). For example, in vitro studies demonstrated that fucoidan can inhibit cell proliferation and induce cell death in numerous cell lines, including human bile duct cancers (8), nonsmall-cell bronchopulmonary carcinoma (9) and lymphoma (10).…”

“…For example, in vitro studies demonstrated that fucoidan can inhibit cell proliferation and induce cell death in numerous cell lines, including human bile duct cancers (8), nonsmall-cell bronchopulmonary carcinoma (9) and lymphoma (10). It is also reported to inhibit the invasion of HT1080 human fibrosarcoma cells and the angiogenic activity of HeLa human uterine carcinoma cells (11). In vivo studies have also demonstrated that fucoidan is a potent anti-neoplastic compound; and is reported to suppress the growth of Ehrlich ascites carcinoma (12,13), Lewis lung carcinoma and B16 melanoma (14), and also inhibit the metastasis of 13762 MAT rat mammary adenocarcinoma (15).…”