Institute of Fisheries Sciences, Pukyong National University, Gijang-gun, Busan 619-911, Republic of Korea.
Int J Oncol. 2013 Oct;43(4):1059-65. doi: 10.3892/ijo.2013.2055. Epub 2013 Aug 7.
Seaweeds are commonly used as functional foods and drugs. A glycoprotein (GP) from the green alga Capsosiphon fulvescens (Cf) has been reported to have antitumor activity toward various cancer cells. We previously observed that Cf-GP induced different pathways of apoptosis in AGS human gastric cancer cells. Transforming growth factor (TGF)-β1 plays an important role in cancer cell migration. Increased TGF-β1 levels increase the expression of the small GTPases and activate the FAK/PI3K/AKT pathways, resulting in the upregulation of integrin receptor proteins, which mediate the attachment of cells to surrounding tissues, cells or extracellular matrix. Thus, the inhibition of TGF-β1 signaling would downregulate integrin expression and thereby effectively decrease cell growth and migration. In the present study, we determined the effect of Cf-GP treatment on the proliferation, migration and apoptosis of AGS human gastric cancer cells. To investigate the mechanism by which Cf-GP exerts its anticancer actions, we examined the effect of Cf-GP on the expression levels of TGF-β1, FAK, PI3K, AKT, the small GTPases and integrins in AGS cells. Our findings indicate that Cf-GP inhibits AGS cell proliferation and migration by downregulating integrin expression via the TGF-β1-activated FAK/PI3K/AKT pathways. These results suggest that Cf-GP may be an important factor in the development of functional foods and therapeutic agents.
海藻通常被用作功能性食品和药物。已报道来自绿藻角叉菜(Capsosiphon fulvescens)的糖蛋白(GP)对各种癌细胞具有抗肿瘤活性。我们之前观察到 Cf-GP 诱导 AGS 人胃癌细胞发生不同的凋亡途径。转化生长因子(TGF)-β1 在癌细胞迁移中发挥重要作用。TGF-β1 水平的增加会增加小 GTPases 的表达并激活 FAK/PI3K/AKT 途径,导致整合素受体蛋白的上调,从而介导细胞与周围组织、细胞或细胞外基质的附着。因此,抑制 TGF-β1 信号会下调整合素的表达,从而有效降低细胞生长和迁移。在本研究中,我们确定了 Cf-GP 处理对 AGS 人胃癌细胞增殖、迁移和凋亡的影响。为了研究 Cf-GP 发挥抗癌作用的机制,我们研究了 Cf-GP 对 AGS 细胞中 TGF-β1、FAK、PI3K、AKT、小 GTPases 和整合素表达水平的影响。我们的研究结果表明,Cf-GP 通过 TGF-β1 激活的 FAK/PI3K/AKT 途径下调整合素表达,从而抑制 AGS 细胞增殖和迁移。这些结果表明 Cf-GP 可能是功能性食品和治疗剂开发的重要因素。