Brown Algae-Derived Fucoidan Exerts Oxidative Stress-Dependent Antiproliferation on Oral Cancer Cells
Journal
Antioxidants (Basel, Switzerland)
Journal Volume
11
Journal Issue
5
Date Issued
2022-04-26
Author(s)
Shiau, Jun-Ping
Chuang, Ya-Ting
Yang, Kun-Han
Chang, Fang-Rong
Sheu, Jyh-Horng
Hou, Ming-Feng
Tang, Jen-Yang
Chang, Hsueh-Wei
Abstract
Fucoidan 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.
Subjects
algae; dietary natural product; fucoidan; oral cancer; oxidative stress; polysaccharide
SDGs
Publisher
MDPI
Type
journal article