Abstract
Fucoidan compounds may increase immune activity and are known to have cancer inhibitory effects in vitro and in vivo. In this study, we aimed to investigate the effect of fucoidan compounds on ex vivo human peripheral blood mononuclear cells (PBMCs), and to determine their cancer cell killing activity both solely, and in combination with an immune-checkpoint inhibitor drug, Nivolumab. Proliferation of PBMCs and interferon gamma (IFNγ) release were assessed in the presence of fucoidan compounds extracted from Fucus vesiculosus, Undaria pinnatifida and Macrocystis pyrifera. Total cell numbers and cell killing activity were assessed using a hormone resistant prostate cancer cell line, PC3. All fucoidan compounds activated PBMCs, and increased the effects of Nivolumab. All fucoidan compounds had significant direct cytostatic effects on PC3 cells, reducing cancer cell numbers, and PBMCs exhibited cell killing activity as measured by apoptosis. However, there was no fucoidan mediated increase in the cell killing activity. In conclusion, fucoidan compounds promoted proliferation and activity of PBMCs and added to the effects of Nivolumab. Fucoidan compounds all had a direct cytostatic effect on PC3 cells, as shown through their proliferation reduction, while their killing was not increased.
Highlights
We focused on the effects of fucoidans from three different species (Fucus vesiculosus, Undaria pinnatifida and Macrocystis pyrifera) alone, and in combination with a T cell activator, and an immune-checkpoint inhibitors (ICI) (Nivolumab, anti-programmed cell death 1 (PD-1)) on human peripheral blood mononuclear cells (PBMCs) and a hormone resistant prostate cancer cell line, PC-3
In order to see whether fucoidans could promote or suppress the activation and proliferation of PBMCs, cell confluence and IFNγ level were quantified in the absence and presence of αCD3
PBMCs and supportthe thekilling killingofofprostate proscancer cells, we looked at changes in theinIFNγ released levellevel for the immune/tumor tate cancer cells, we looked at changes the IFNγ released for the immune/tumorcoculture
Summary
Fucoidans are a class of brown seaweed derived, fucose rich sulfated polysaccharides that are known to have direct and indirect effects on cancer cells in vitro and in vivo [1,2,3,4]. On the one hand, to be ‘anti-inflammatory’ [2,12]. Fucoidan is classically known as a selectin and scavenger receptor blocking agent [13]. By blocking these cellular adhesion molecules, fucoidan can prevent intrusion of neutrophils into tissue spaces, attenuating inflammatory responses. Fucoidans may act as immune adjuvants [14,15], recover immunity in immunosuppressed mice [16] and stimulate chemokines, major histocompatibility complex class I and II, and pro-inflammatory cytokines in PBMCs [17]
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