Shiau, Jun-PingJun-PingShiauChuang, Ya-TingYa-TingChuangYang, Kun-HanKun-HanYangChang, Fang-RongFang-RongChangSheu, Jyh-HorngJyh-HorngSheuHou, Ming-FengMing-FengHouJIIANG-HUEI JENGTang, Jen-YangJen-YangTangChang, Hsueh-WeiHsueh-WeiChang2023-05-042023-05-042022-04-262076-3921https://scholars.lib.ntu.edu.tw/handle/123456789/630833Fucoidan is a dietary brown algae-derived fucose-rich polysaccharide. However, the anticancer effects of fucoidan for oral cancer treatment remain unclear, particularly in terms of its preferential antiproliferation ability and oxidative-stress-associated responses. This study first evaluated the effects and mechanisms of the preferential antiproliferation of fucoidan between oral cancer and non-malignant oral cells (S-G). In a 48 h MTS assay, fucoidan showed higher antiproliferation in response to five types of oral cancer cells, but not S-G cells, demonstrating preferential antiproliferation of oral cancer cells. Oral cancer cells (Ca9-22 and CAL 27) showing high sensitivity to fucoidan were selected to explore the antiproliferation mechanism compared to S-G cells. Fucoidan showed subG1 accumulation and an annexin V increase in apoptosis, accompanied by caspase 8, 9, and 3 activations in oral cancer cells, but not in S-G cells. Fucoidan increased reactive oxygen species and mitochondrial superoxide levels and decreased cellular glutathione in oral cancer cells compared with S-G cells. These oxidative stress effects were attributed to the downregulation of antioxidant signaling genes (NRF2, TXN, and HMOX1) in oral cancer cells rather than S-G cells. Fucoidan showed DNA damage-inducible effects (γH2AX and 8-hydroxy-2-deoxyguanosine) in oral cancer cells but not in S-G cells. Accordingly, these preferential changes in oral cancer but not in non-malignant cells contribute to the preferential antiproliferation mechanism of fucoidan. Furthermore, these changes were reverted by pretreatment with the antioxidant N-acetylcysteine. Therefore, for the first time, this study provides a detailed understanding of the preferential antiproliferation effects and mechanisms of fucoidan in oral cancer cells.enalgae; dietary natural product; fucoidan; oral cancer; oxidative stress; polysaccharide[SDGs]SDG3journal article10.3390/antiox11050841356247052-s2.0-85128707570WOS:000801665900001https://api.elsevier.com/content/abstract/scopus_id/85128707570