Fucoidan inhibits proliferation of the SKM-1 acute myeloid leukaemia cell line via the activation of apoptotic pathways and production of reactive oxygen species

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and a high risk of progression to acute myeloid leukaemia (AML). Fucoidan, a complex sulphated polysaccharide isolated from the cell wall of brown seaweeds, has recently attracted attention for its multiple biological activities and its potential as a novel candidate for cancer therapy. In the present study, the anti-cancer activity of fucoidan was investigated in the MDS/AML cell line SKM-1. Fucoidan inhibited proliferation, induced apoptosis and caused G1-phase arrest of the cell cycle in SKM-1 cells as determined by a cell counting kit 8 assay and flow cytometry. Furthermore, reverse transcription quantitative polymerase chain reaction and western blot analyses indicated that treatment with fucoidan (100 µg/ml for 48 h) activated Fas and caspase-8 in SKM-1 cells, which are critical for the extrinsic apoptotic pathway; furthermore, caspase-9 was activated via decreases in phosphoinositide-3 kinase/Akt signaling as indicated by reduced levels of phosphorylated Akt, suggesting the involvement of the intrinsic apoptotic pathway. In addition, fucoidan treatment of SKM-1 cells resulted in the generation of reactive oxygen species (ROS) as determined by staining with dichloro-dihydro-fluorescein diacetate. These results suggested that the mechanisms of the anti-cancer effects of fucoidan in SKM-1 are closely associated with cell cycle arrest and apoptotic cell death, which partly attributed to the activation of apoptotic pathways and accumulation of intracellular ROS. Our results demonstrated that Fucoidan inhibits proliferation and induces the apoptosis of SKM-1 cells, which provides substantial therapeutic potential for MDS treatment.

Silencing Prion Protein in HT29 Human Colorectal Cancer Cells Enhances Anticancer Response to Fucoidan

“…Moreover, proapoptotic BAX, cleaved caspase-3, and cleaved PARP1 increased while BCL2 decreased upon fucoidan treatment of HT29 cells, stimulating cell death. These results are supported by previous studies in which fucoidan inhibited proliferation of myeloid leukemia cell lines, mediated by activation of apoptotic pathways (21). Therefore, our results strongly suggest that fucoidan plays an ANTICANCER RESEARCH 36: 4449-4458 (2016) 4454 important role in HT29 cell-cycle arrest and apoptosis.…”

Fucoidan induces Toll-like receptor 4-regulated reactive oxygen species and promotes endoplasmic reticulum stress-mediated apoptosis in lung cancer

“…Importantly, we demonstrated that fucoidan induces ROS in a very short period (within 30 min). In contrast, fucoidan has been reported to promote mitochondrial-derived ROS generation after approximately 24–48 h25. Thus, the fucoidan-induced increase in ROS may occur at an early stage (receptor-mediated) or at a later stage (mitochondria-derived).…”

“…However, there are many “factors” of fucoidan involved in anti-cancer functions; for example, sources of fucoidan (species of brown seaweeds)232425, effective concentration, structural characteristics, sulfate content, molecular weight, purity, isolation/extraction methods, etc., as well as importantly the kind of cancer cells to be tested. Here, using HiQ-fucoidan from Laminaria japonica , we found that fucoidan also prevents and inhibits lung tumor growth at higher concentrations (Supplementary Fig.…”

“…In addition, evidence of the involvement of ROS in a variety of fucoidan and induced apoptosis has been accumulated; for example, fucoidan of the Mozuku seaweed ( Cladosiphon novae - caledoniae Kylin) activates a caspase-independent apoptotic pathway in human MCF-7 breast cancer cells through ROS-dependent JNK activation and the mitochondria-mediated Bcl-2 family pathways23; fucoidan ( Undaria pinnatifida sporophylls) induces apoptosis in human SMMC-7721 hepatocellular carcinoma via the ROS-mediated mitochondrial pathway and activation of caspases process24; and fucoidan ( Fucus vesiculosus ) inhibits proliferation of human myelodysplastic syndrome/acute myeloid leukemia cell line SKM-1 via the activation of apoptotic pathways and production of ROS25. However, the mechanism by which fucoidan-induced extracellular signaling induces ER stress and ROS remains unclear.…”

Tubeimoside-1 induces oxidative stress-mediated apoptosis and G0/G1 phase arrest in human prostate carcinoma cells in vitro

“…Recent research has shown that in contrast to the tumor-promoting ability of higher ROS levels, this biochemical property of cancer cells may have therapeutic benefits. Targeting mitochondria to increase the ROS level above a toxic threshold by exogenous ROS-generating phytochemicals to selectively kill cancer cells has been shown to be feasible in various in vitro and in vivo experimental models [29][30][31][32][33] . In the present study, TBMS1 increased ROS generation, modulated Bax and Bcl-2 expression, dissipated mitochondrial membrane potential and ultimately induced apoptosis in DU145 cells by inducing DNA fragmentation and caspase-3 cleavage in a dose-dependent manner.…”