A polysaccharide from Arthrospira platensis alleviates pancreatic cancer associated with negatively regulating galectin-3 and glypican-6 expression

Pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) is one of the most common malignancies and the leading cause of cancer-related death worldwide. Hence, there is an urgent need to explore new anti-pancreatic cancer agents. This study shows a novel homogeneous polysaccharide named ESPPW from Arthrospira platensis. The molecular weight of ESPPW is estimated as 356 kDa, and it is mainly composed of glucose and rhamnose, with minor mannose, glucuronic acid, galacturonic acid, galactose, xylose, arabinose, and fucose. ESPPW may impair the growth and migration of PDAC cells in vitro and in vivo. Mechanism study demonstrates that ESPPW induces the pro-apoptotic caspase-3 activation and is associated with an up-regulation of tumor-suppressor p53 proteins expression. Interestingly, the expressions of galectin-3 (Gal-3) and glypican-6 (GPC-6) are significantly downregulated by 2.8 nM of ESPPW in a time-dependent manner. At the same time, immunohistochemical analysis of tumor xenograft tissue results supports these findings. We further show that over-expression of Gal-3 and GPC-6 rescues the apoptotic effect indicated by CDK2 expression induced by ESPPW. In conclusion, these data demonstrate that ESPPW impedes PDAC cell growth by inducing cell apoptosis and interrupting Gal-3 and GPC-6 function.