Abstract
Fucoidans, fucose-enriched sulfated polysaccharides isolated from brown algae and marine invertebrates, have been shown to exert anticancer activity in several types of human cancer, including leukemia and breast cancer and in lung adenocarcinoma cells. In the present study, the anticancer activity of the fucoidan extracted from the brown seaweed Undaria pinnatifida was investigated in human hepatocellular carcinoma SMMC-7721 cells, and the underlying mechanisms of action were investigated. SMMC-7721 cells exposed to fucoidan displayed growth inhibition and several typical features of apoptotic cells, such as chromatin condensation and marginalization, a decrease in the number of mitochondria, and in mitochondrial swelling and vacuolation. Fucoidan-induced cell death was associated with depletion of reduced glutathione (GSH), accumulation of high intracellular levels of reactive oxygen species (ROS), and accompanied by damage to the mitochondrial ultrastructure, depolarization of the mitochondrial membrane potential (MMP, Δψm) and caspase activation. Moreover, fucoidan led to altered expression of factors related to apoptosis, including downregulating Livin and XIAP mRNA, which are members of the inhibitor of apoptotic protein (IAP) family, and increased the Bax-to-Bcl-2 ratio. These findings suggest that fucoidan isolated from U. pinnatifida induced apoptosis in SMMC-7721 cells via the ROS-mediated mitochondrial pathway.
Highlights
Fucoidans are a class of fucose-enriched sulfated polysaccharides primarily extracted from brown seaweeds [1,2]
To determine whether the changes in reactive oxygen species (ROS) accumulation were related to GSH depletion or a decline in total anti-oxidant capability (T-AOC), we investigated the effects of fucoidan on intracellular GSH and T-AOC in SMMC-7721 cells using commercial colorimetric assays
This study demonstrated that the fucoidan downregulated the expression of XIAP and Livin mRNA, which was associated with activation of caspase-3 and caspase-9, indicating that fucoidan-induced apoptosis occurred via the mitochondrial pathway
Summary
Fucoidans are a class of fucose-enriched sulfated polysaccharides primarily extracted from brown seaweeds [1,2]. Low physiological levels of ROS serve as a signaling messenger to mediate various biological responses, including cell proliferation, angiogenesis, innate immunity, gene expression, apoptosis and senescence [18]. It has been established that increased levels of these short-lived reactive molecules can exert harmful effects by inducing oxidative damage to biological macromolecules and disrupting the cellular reduction-oxidation (redox) balance. Such disturbances to ROS homeostasis are generally considered to be a risk factor for the initiation and progression of diseases such as atherosclerosis, neurodegeneration and cancer [19]. U. pinnatifida sporophylls in human HCC SMMC-7721 cells, and investigate the molecular mechanisms of these effects
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