Inhibitory effect of Sargassum latifolium extract on hypoxia pathway in colon cancer cells

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.

Automated summary

The water-soluble polysaccharide extract fractions SL1 and SL4 from Sargassum latifolium exhibited cytotoxic effects on HCT-116 cells by enhancing apoptosis and inhibiting total cell hypoxia. These fractions also significantly suppressed the expression of hypoxia regulators miRNA-21 and miRNA-210.