Fucoidan Independently Enhances Activity in Human Immune Cells and Has a Cytostatic Effect on Prostate Cancer Cells in the Presence of Nivolumab

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 (IFNg) 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.

Immunopotentiating Activity of Fucoidans and Relevance to Cancer Immunotherapy

“…Furthermore, the combination treatment inhibits the infiltration of B16 tumor cells into the lung and prevents the growth of metastatic murine colon carcinoma CT-26 tumors in the lung [ 23 ]. When fucoidan was used together with Nivolumab, it increased the effects of Nivolumab on prostate cancer cells by enhancing the activity of human immune cells, and an additive effect was observed [ 136 ]. In a murine tumor model, a combination of fucoidan and anti-PD-L1 antibody inhibited CT-26 tumor growth more effectively than the anti-PD-L1 antibody.…”

“…Fucoidan extracts from three types of species ( Fucus vesiculosus , Undariia pinnatifidat , Macrocystis pyrifera ) are capable of independently promoting the activation and proliferation of human peripheral blood mononuclear cells (PBMC) in the presence of a T cell activator (anti-CD3) by increasing IFN- production. In these studies, fucoidan derived from Fucus vesiculosus was the optimal fucoidan based on the potency of these three different types of fucoidan [ 136 ]. Moreover, fucoidan induced antitumor effects by stimulating DC maturation and/or macrophage differentiation.…”

Anti-Proliferative and Pro-Apoptotic vLMW Fucoidan Formulas Decrease PD-L1 Surface Expression in EBV Latency III and DLBCL Tumoral B-Cells by Decreasing Actin Network

“…Fucoidan extracted from Fucus vesiculosus promoted activation of tumor-infiltrating CD8 + T-cells and strongly inhibited growth of melanoma cells when co-administrated with anti-PD-1, particularly when applied before immunotherapy [ 35 ]. Fucoidan extracted from three species of algae, among them Fucus vesiculosus , promoted proliferation and activity of ex vivo PBMCs and potentiated anti-PD-1 effects [ 68 ]. Intranasal administration of Ecklonia-cava -extracted fucoidan enhanced anti-PD-L1 mediated anti-cancer activities against melanoma and carcinoma tumor growth in lungs [ 69 ].…”

Functional immune boosters; the herb or its dead microbiome? Antigenic TLR4 agonist MAMPs found in 65 medicinal roots and algae’s

“…(Gammaproteobacteria) bacteroidetes and Alphaproteobacteria and coincide with efficacy of brown seaweeds such as bladderwrack ( Fucus vesiculosus ) which also bestow tumor suppressive effects ( Gupta et al, 2020 ), on ovarian ( Bae et al, 2020 ) estrogen-dependent cancers ( Zhang et al, 2016 ) head and neck ( Blaszczak et al, 2018 ), thyroid ( Shen et al, 2017 ) and pancreatic cancers ( Geisen et al, 2015 ). These studies all show a pattern by which medicinal use of sea plants can evoke stimulation of natural killer (NK) cells ( Zhang et al, 2021b ) or greater peripheral blood mononuclear cell counts ( Park et al, 2021 ). These heavily laden microbial reservoirs have been consumed for centuries, with a plethora of recent research showing the same to instill anti-tumor immunity ( Ishiguro et al, 2020 ; Skjanes et al, 2021 ) in various cancers including colon, breast ( Yuan and Walsh, 2006 ), hormone-related ( Skibola et al, 2005 ) and thyroid ( Rosen et al, 2014 ).…”