Enzyme-digested fucoidan extracts derived from seaweed Mozuku of Cladosiphon novae-caledoniae kylin inhibit invasion and angiogenesis of tumor cells

Enzyme-digested fucoidan extracts derived from seaweed Mozuku of Cladosiphon novae-caledoniae kylin inhibit invasion and angiogenesis of tumor cells
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DOI:
10.1007/s10616-005-3761-8
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发表时间:
2005-01-01
期刊:
影响因子:
2.2
通讯作者:
Shirahata, S
Shirahata, S
中科院分区:
生物学4区
文献类型:
--
作者:
Ye, J;Li, YP;Shirahata, S

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岩藻依聚糖是在几种类型的褐藻的细胞壁中发现的一种非结构的硫酸化多糖,其最近,特别是作为酶消化的岩藻依聚糖提取物,由于其抗肿瘤潜力而引起了很多关注。在这项研究中,我们评估了酶消化的褐藻糖胶提取物制备的海藻Mozuku的枝管藻-caledikylin在体外侵袭和血管生成能力的人肿瘤细胞的影响。首先,我们评估了岩藻依聚糖提取物对肿瘤细胞氧化应激的影响,并证明了岩藻依聚糖提取物处理后,细胞内H2 O2水平和肿瘤细胞释放的H2 O2均被极大地抑制,表明岩藻依聚糖提取物改善了肿瘤细胞的氧化应激。接下来,我们测试了岩藻依聚糖提取物对人纤维肉瘤HT 1080细胞侵袭能力的影响,表明岩藻依聚糖提取物显著抑制其侵袭,可能是通过抑制基质金属蛋白酶(MMP)MMP-2/9活性。此外,我们研究了岩藻依聚糖提取物对人子宫癌HeLa细胞的血管生成的影响,并且发现岩藻依聚糖提取物抑制血管生成因子血管内皮生长因子(VEGF)的表达和分泌,导致抑制肿瘤细胞的血管小管形成。综合以上结果,阐明了枝管藻中的酶解岩藻依聚糖提取物对肿瘤细胞的侵袭和血管生成具有抑制作用。这些影响可能,至少部分地,引起酶消化岩藻依聚糖提取物的抗氧化潜力。
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 H2O2 level and released H2O2 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.