Abstract
Sargassum latifolium, (Turner) C. Agarth, 1820, is an edible brown alga that was collected from red seashores in Egypt. Colon cancer is a lethal disease world-wide. Hypoxia is a key player in progressive colon tumor growth and stemness. This work was planned to extract water-soluble polysaccharide from S. latifolium, to separate its fractions (SL1, SL2, SL3, and SL4) and hence to investigate their antihypoxia characteristics in colon cancer HCT-116 cells. Algal fractions cytotoxicity was assayed by MTT; DNA staining was used to analyze apoptosis and necrosis; total hypoxia status was assessed by pimonidazole, HIF-1 alpha and HIF-1 beta were estimated by ELISA, and hsa-miRNA21-5p and hsa-miRNA-210-3p were analyzed by qPCR. The results indicated that SL1 and SL4 are cytotoxic agents against HCT-116 cells through enhancing apoptosis. SL1 and SL4 were potent inhibitor of total cell hypoxia (p < 0.001). Both fractions significantly suppressed the expression of miR-21 (p < 0.01) and miR-210 (p < 0.001), and the concentration of HIF-1 alpha protein (p < 0.01 and p < 0.001, respectively), while only SL1 inhibited HIF-1 beta protein concentration (p < 0.05). Taken together S. latifolium polysaccharide extract fractions SL1 and SL4 exhibited anti-hypoxic property in HCT-116 cells through mechanistic role in the expression of hypoxia regulators miRNA-21 and miRNA-210, and accordingly in HIF-1 alpha and HIF-1 beta biosynthesis.