Department of Pharmacology, School of Medicine, Jeju National University, 102 Jejudaehakno, Jeju 690-756, Korea.
Mar Drugs. 2013 Aug 19;11(8):2982-99. doi: 10.3390/md11082982.
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.
岩藻聚糖硫酸酯是一种硫酸化多糖,具有多种生物活性,如抗癌、抗血管生成和抗炎作用。然而,岩藻聚糖硫酸酯作为抗癌剂的作用机制尚未完全阐明。本研究探讨了从裙带菜中提取的岩藻聚糖硫酸酯对人前列腺癌细胞 PC-3 的抗癌作用。岩藻聚糖硫酸酯通过激活内在和外在途径诱导 PC-3 细胞凋亡。凋亡的诱导伴随着细胞外信号调节激酶丝裂原激活蛋白激酶 (ERK1/2 MAPK) 的激活和 p38 MAPK 和磷脂酰肌醇 3-激酶 (PI3K)/Akt 的失活。此外,岩藻聚糖硫酸酯还诱导 p21Cip1/Waf 的上调和细胞周期相关蛋白 E2F-1 的下调。此外,在 Wnt/β-catenin 通路中,岩藻聚糖硫酸酯激活 GSK-3β,导致β-catenin 水平降低,随后 c-myc 和 cyclin D1 表达降低,β-catenin 在 PC-3 细胞中的靶基因。这些结果表明,岩藻聚糖硫酸酯处理可能通过激活 ERK1/2 MAPK、失活 p38 MAPK 和 PI3K/Akt 信号通路以及下调 Wnt/β-catenin 信号通路,诱导 PC-3 前列腺癌细胞的内在和外在凋亡途径。这些数据支持岩藻聚糖硫酸酯可能具有治疗前列腺癌的潜力。