Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan; Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202, Taiwan.
Section of Urology, Cheng-Hsin Rehabilitation Medical Center, Taipei 112, Taiwan.
Int J Biol Macromol. 2022 Nov 30;221:623-633. doi: 10.1016/j.ijbiomac.2022.09.047. Epub 2022 Sep 11.
A variety of anticancer activities have been established for fucoidan from brown algae, whereas whether cancer stem cells (CSCs) are inhibited by sulfated polysaccharides is unexplored. In this study, fucoidan extracted from Sargassum hemiphyllum was showed heat stable and might tolerate 140 °C treatment. Fucoidan did not exhibit cytotoxicity in 5637 and T24 bladder cancer cells. After fucoidan treatment, the stress fibers were aggregated into thick and abundant underneath the plasma membrane and getting around the cells, and the structure of F-actin showed a remarkable change in the filopodial protrusion in T24 and 5637 cells. Using culture inserts, transwell assays and time lapse recordings showed that fucoidan inhibited cell migration. In the epithelial-mesenchymal transition (EMT), fucoidan downregulated the expression of vimentin, a mesenchymal marker, and upregulated the expression of E-cadherin, an epithelial marker. Additionally, the transcription levels of Snail, Slug, Twist1, Twist2, MMP2 and MMP9 were significantly decreased by fucoidan, indicating EMT suppression. CSCs are implicated in tumor initiation, metastatic spread, drug resistance and tumor recurrence. Our results showed that fucoidan inhibited stemness gene expression and sphere formation in bladder CSCs. For the first time, our findings demonstrated that fucoidan inhibits CSC formation and provides evidence as potential anticancer therapy.
从褐藻中提取的岩藻聚糖具有多种抗癌活性，而硫酸多糖是否抑制癌症干细胞（CSC）尚未得到探索。在这项研究中，从半叶马尾藻中提取的岩藻聚糖具有热稳定性，可能耐受 140°C 的处理。岩藻聚糖在 5637 和 T24 膀胱癌细胞中没有表现出细胞毒性。岩藻聚糖处理后，应力纤维聚集在质膜下方并包裹细胞，形成厚而丰富的结构，在 T24 和 5637 细胞的丝状伪足突起中，F-肌动蛋白的结构发生了显著变化。使用培养插入物、Transwell 测定和延时记录表明岩藻聚糖抑制细胞迁移。在上皮-间充质转化（EMT）中，岩藻聚糖下调了间充质标志物波形蛋白的表达，并上调了上皮标志物 E-钙粘蛋白的表达。此外，岩藻聚糖显著降低了转录因子 Snail、Slug、Twist1、Twist2、MMP2 和 MMP9 的转录水平，表明 EMT 受到抑制。CSC 参与肿瘤起始、转移扩散、耐药和肿瘤复发。我们的研究结果表明，岩藻聚糖抑制膀胱 CSC 的干性基因表达和球体形成。这是首次表明岩藻聚糖抑制 CSC 形成，并为潜在的抗癌治疗提供了证据。
