Wang Yun, Liu Ge, Liu Rui, Wei Maosheng, Zhang Jinxiang, Sun Chaomin
CAS and Shandong Province Key Laboratory of Experimental Marine Biology & Center of Deep Sea Research, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China.
Mar Drugs. 2021 Mar 22;19(3):171. doi: 10.3390/md19030171.
The prognosis of liver cancer was inferior among tumors. New medicine treatments are urgently needed. In this study, a novel exopolysaccharide EPS364 was purified from 364, which was isolated from a deep-sea cold seep of the South China Sea. Further research showed that EPS364 consisted of mannose, glucosamine, gluconic acid, galactosamine and arabinose with a molar ratio of 5:9:3.4:0.5:0.8. The relative molecular weight of EPS364 was 14.8 kDa. Our results further revealed that EPS364 was a β-linked and phosphorylated polysaccharide. Notably, EPS364 exhibited a significant antitumor activity, with inducing apoptosis, dissipation of the mitochondrial membrane potential (MMP) and generation of reactive oxygen species (ROS) in Huh7.5 liver cancer cells. Proteomic and quantitative real-time PCR analyses indicated that EPS364 inhibited cancer cell growth and adhesion via targeting the FGF19-FGFR4 signaling pathway. These findings suggest that EPS364 is a promising antitumor agent for pharmacotherapy.
肝癌在各类肿瘤中预后较差。迫切需要新的药物治疗方法。在本研究中,从南海深海冷泉分离出的菌株364中纯化得到一种新型胞外多糖EPS364。进一步研究表明,EPS364由甘露糖、氨基葡萄糖、葡萄糖酸、半乳糖胺和阿拉伯糖组成,摩尔比为5:9:3.4:0.5:0.8。EPS364的相对分子质量为14.8 kDa。我们的结果进一步表明,EPS364是一种β-连接的磷酸化多糖。值得注意的是,EPS364表现出显著的抗肿瘤活性,可诱导Huh7.5肝癌细胞凋亡、线粒体膜电位(MMP)消散和活性氧(ROS)生成。蛋白质组学和定量实时PCR分析表明,EPS364通过靶向FGF19-FGFR4信号通路抑制癌细胞生长和黏附。这些发现表明,EPS364是一种有前景的用于药物治疗的抗肿瘤药物。