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Abstract
Fucoidan, a sulfated polysaccharide, has a variety of biological activities, such as anti-cancer, anti-angiogenic and anti-inflammatory. However, the mechanisms of action of fucoidan as an anti-cancer agent have not been fully elucidated. The present study examined the anti-cancer effect of fucoidan obtained from Undaria pinnatifida in PC-3 cells, human prostate cancer cells. Fucoidan induced the apoptosis of PC-3 cells by activating both intrinsic and extrinsic pathways. The induction of apoptosis was accompanied by the activation of extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK) and the inactivation of p38 MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt. In addition, fucoidan also induced the up-regulation of p21Cip1/Waf and down-regulation of E2F-1 cell-cycle-related proteins. Furthermore, in the Wnt/β-catenin pathway, fucoidan activated GSK-3β that resulted in the decrease of β-catenin level, followed by the decrease of c-myc and cyclin D1 expressions, target genes of β-catenin in PC-3 cells. These results suggested that fucoidan treatment could induce intrinsic and extrinsic apoptosis pathways via the activation of ERK1/2 MAPK, the inactivation of p38 MAPK and PI3K/Akt signaling pathway, and the down-regulation of Wnt/β-catenin signaling pathway in PC-3 prostate cancer cells. These data support that fucoidan might have potential for the treatment of prostate cancer.
Highlights
Fucoidan is a sulfated polysaccharide found in the cell wall matrix of brown seaweed, such as Ascophyllum nodosum, Cladosiphon okamuranus, Ecklonia kurome, Fucus evanescens, Fucus vesiculosus, Hizikia fusiforme, Laminaria angustata and Undaria pinnatifida [1,2,3]
(10 μg/mL, 15.2%; 50 μg/mL, 29.8%; 100 μg/mL, 39.3%; 200 μg/mL, 45.1%) (Figure 1). These results indicate that fucoidan could inhibit the growth of PC-3 cells in a dose-dependent manner
We investigated whether the inhibitory effect of fucoidan on the growth of the PC-3 cells resulted from apoptosis induction
Summary
Fucoidan is a sulfated polysaccharide found in the cell wall matrix of brown seaweed, such as Ascophyllum nodosum, Cladosiphon okamuranus, Ecklonia kurome, Fucus evanescens, Fucus vesiculosus, Hizikia fusiforme, Laminaria angustata and Undaria pinnatifida [1,2,3]. The up-regulation of the Wnt/β-catenin pathway has been found in a large portion of prostate cancer patients in several reports [14]. The increased expression of β-catenin, a key component of the canonical Wnt signaling pathway, plays a pivotal role in many cancers. In the absence of a Wnt signal, the β-catenin level is constitutively decreased by a β-catenin degradation complex, including axin, adenomatous polyposis coli (APC), casein kinase I and GSK-3β [16]. Destruction complex, GSK-3β plays a pivotal role in the Wnt pathway. Wnt signaling, which may contribute to the progression of prostate cancer [17]. The present study demonstrates the anticancer effect of fucoidan on apoptosis induction by the down-regulation of the Wnt/β-catenin pathway in PC-3 human prostate cancer cells
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