Sulfated polysaccharides from Padina tetrastromatica arrest cell cycle, prevent metastasis and downregulate angiogenic mediators in HeLa cells

Development of therapeutic agents that can inhibit cell cycle, metastasis and angiogenesis in cancer cells is now emerging as a crucial strategy for cancer management. Some marine derived compounds such as sulfated polysaccharides were found to possess all these properties and hence they can be exploited well for these therapeutic applications. Based on this background, the current study focuses on the cell cycle arresting, anti metastatic and anti angiogenic activities of marine algal derived sulfated polysaccharides. Sulfated polysaccharides have been isolated and purified from the marine algae Padina tetrastromatica and named as Ethanolic Sulfated Polysaccharides-Column Purified (ESPs-CP). They were then evaluated for various anticancer effects in HeLa cells. Count and viability assay and cell cycle analysis were done using flow cytometry and other studies include scratch wound assay, CAM assay and gene expression. ESPs-CP successfully arrested cell cycle at G0/G1 phase and the effect was mediated through the upregulated expression of P21 and down regulation of cyclin D. The scratch wound assay revealed the inhibitory effect of ESPs-CP on the migration of HeLa cells. The two important mediators of metastasis, MMP2 and MMP9 were downregulated by ESPs-CP. During CAM assay, ESPs-CP suppressed the development of new blood vessels and reduced the hemoglobin content. They have also downregulated the expression of angiogenic mediators such as VEGF and HIF1A in HeLa cells. Thus ESPs-CP can be considered as a potent therapeutic agent for the management of cancer.