AUTHOR=Gamal-Eldeen Amira M. , Raafat Bassem M. , Alrehaili Amani A. , El-Daly Sherien M. , Hawsawi Nahed , Banjer Hamsa J. , Raafat Eman M. , Almehmadi Mazen M. TITLE=Anti-hypoxic Effect of Polysaccharide Extract of Brown Seaweed Sargassum dentifolium in Tongue Squamous Cell Carcinoma JOURNAL=Frontiers in Nutrition VOLUME=Volume 9 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.854780 DOI=10.3389/fnut.2022.854780 ISSN=2296-861X ABSTRACT=Sargassum dentifolium, ‎(Turner) C. Agarth, 1820, is an edible brown alga collected from red ‎seashores, Egypt. Oral tongue squamous cell carcinoma (OTSCC) is an aggressive malignancy. ‎Hypoxia leads to chemotherapeutic resistance. This work aimed to explore the anti-hypoxia effect of ‎water-soluble polysaccharide fractions of S. dentifolium (SD1-SD3), in CAL-27 OTSCC cells. Cell ‎cytotoxicity assay (MTT); cell death mode (DNA staining); total hypoxia (pimonidazole), HIF-1α ‎‎(ELISA and immunocytochemistry), HIF-1β (ELISA), and hsa-miRNA-21-5p and hsa-miRNA-210-3p ‎‎(qRT-PCR) were investigated. SD1 and SD2 showed a cytotoxic effect due to apoptosis. SD2 and ‎SD3 decreased total cell hypoxia, inhibited miR-210 (p<0.001 and p<0.01), miR-21 (p<0.01 and ‎p<0.05), and HIF-1α (p<0.01 and p<0.05), respectively. However, only SD3 suppressed HIF-1β ‎‎(p<0.05). In conclusion, SD2 showed a potential anti-hypoxia effect through amelioration of HIF-1α ‎regulators, which may help in decreasing hypoxia-induced therapeutic resistance‎.‎