Expression data from adult wild-type and transgenic zebrafish revealed Oligo-Fucoidan Prevents Radiation induced fibrosis and secondary tumors in zebrafish
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ABSTRACT: Radiotherapy (RT) often causes unwanted side effects such as radiation-induced fibrosis (RIF) and second malignancies (SM). Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has many biological effects including anti-inflammation and anti-tumor. In the present study, we investigated the radioprotective effect of Oligo-Fucoidan (OF) using zebrafish animal model. Using an oligo-fucoidan oral gavage in wild-type and adult transgenic zebrafish, we then used microarrays to detail the global programme of gene expression after fucoidan treatment and identified distinct classes of up- and down-regulated genes during this process.
Project description:Oligo-fucoidan (OF), a sulfated polysaccharide extracted from brown seaweed, exhibits anti-inflammation and antitumor effects, however, knowledge concerning the detailed mechanism of oligo-fucoidan on liver cells is obscure. In this study, we investigate the effect of oligo-fucoidan in normal hepatocytes using transcriptomic analysis. Using an oligo-fucoidan oral gavage in adult wild-type zebrafish, we then used microarrays to detail the global programme of gene expression after fucoidan treatment and identified distinct classes of up- and down-regulated genes during this process.
Project description:Hepatocellular carcinoma is the fourth leading cause of cancer-related deaths worldwide. Many carcinogens induce inflammation and cirrhosis, and eventually develop into liver cancer. Fucoidan is sulfated polysaccharide that is mainly found in brown seaweeds. In this study, we investigated the effects and mechanisms of low molecular weight fucoidan (i.e. oligo-fucoidan) preventing hepatocarcinogenesis using HBx,Src, and HBx,Src,p53-/+ transgenic zebrafish liver cancer model. Using an oligo-fucoidan oral gavage in adult transgenic zebrafish, we then used microarrays to detail the global programme of gene expression after fucoidan treatment and identified distinct classes of up- and down-regulated genes during this process.
Project description:Expression data from adult wild-type and transgenic zebrafish revealed Oligo-Fucoidan Prevents Radiation induced fibrosis and secondary tumors in zebrafish
Project description:Fucoidan is a high-molecular polysaccharide whose main constituent is sulfated fucose. Extensive studies have demonstrated numerous interesting biological activities for fucoidan. We specifically focused on the anti-proliferation activity of fucoidan and examined the underlying mechanism in MKN45 gastric cancer cells. BrdU assay revealed that fucoidan impeded the MKN45 cell cycle by approximately 50%, and clonogenic assay also showed that fucoidan inhibited cell proliferation. Preliminary examinations of fucoidan using LDH assay showed no immediate cytotoxic effects at 24-h exposure. However, longer time courses revealed inhibition of cell growth at 4 days in a dose-dependent manner. Microarray analysis in MKN45 cells treated with fucoidan identified genes that were upregulated and downregulated in response to fucoidan, including MAP3K5, or ASK1 (apoptosis signal-regulating kinase), which was upregulated by 1.38-fold. Western blot confirmed that fucoidan increased ASK1 protein levels, while reducing the levels of phosphorylated ASK1. Reduction of ASK1 by siRNA decreased proliferation of MKN45 cells. Our findings show that fucoidan may suppress cellular proliferation and DNA synthesis in MKN45 cells by suppressing the ASK1-p38 signaling pathway through reduction of phosphorylated ASK1 levels.
Project description:Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, possesses many biological activities including anti-inflammatory and anti-oxidant activities. We aimed to investigate the protective effects of fucoidan on dyslipidemia and atherosclerosis in apolipoprotein E-deficient mice (ApoEshl mice) and to elucidate its molecular targets in the liver by using a transcriptomic approach. For 12 weeks, ApoEshl mice were fed a high-fat diet (HFD) supplemented with either 1% or 5% fucoidan. Fucoidan supplementation significantly reduced tissue weight (liver and white adipose tissue), blood lipid, total-cholesterol (TC), triglyceride (TG), non-high density lipoprotein-cholesterol (Non-HDL-C), and glucose levels in HFD-fed ApoEshl mice but increased plasma lipoprotein lipase (LPL) activity and HDL-C levels. Fucoidan also reduced hepatic steatosis levels (liver size, TC and TG levels, and lipid peroxidation) and increased white adipose tissue LPL activity. DNA microarray analysis and quantitative reverse transcription-polymerase chain reaction demonstrated differential expression of genes encoding proteins involved in lipid metabolism, energy homeostasis, and insulin sensitivity, by activating Ppara and inactivating Srebf1. Fucoidan supplementation markedly reduced the thickness of the lipid-rich plaque, lipid peroxidation, and foaming macrophage accumulation in the aorta in HFD-fed ApoEshl mice. Thus, fucoidan supplementation appears to have anti-dyslipidemic and anti-atherosclerotic effects by inducing LPL activity and inhibiting the effects of inflammation and oxidative stress in HFD-fed ApoEshl mice.
Project description:Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse reaction of chemotherapy with limited treatment. Previous research indicates neutrophil extracellular traps (NETs) is a critical pathogenesis of CIPN. LPS/HMGB1 serve as important inducers of NETs. Here, we aim to target inhibiting NETs formation (NETosis) to alleviate CIPN. Clinically we found the content of LPS, HMGB1 and NETs in the plasma of CIPN patients was significantly increased and positively correlated with VAS scores. Fucoidan decreased LPS/HMGB1/NETs content and relieved CIPN in mice. Mechanistically, fucoidan upregulated the scavenger receptor A1 (SR-A1) expression and promoted bone marrow derived macrophage (BMDM) to phagocytize LPS/HMGB1. Fucoidan also facilitated BMDM to engulf NETs via the recognition and localization of SR-A1 and HMGB1. The therapeutic effects of fucoidan were abolished by SR-A1 knockout. RNA-seq analysis showed that fucoidan significantly increased sqstm1 (p62) gene expression. Fucoidan promoted the competitive binding of sqstm1 and Nrf2 to Keap1, increasing Nrf2 nuclear translocation and SR-A1 transcription. Additionally, microbial diversity sequencing analysis (16S) showed that fucoidan increased gut microbiota diversity and abundance, and upregulated the Bacteroides/Firmicutes ratio. In conclusion, fucoidan promotes SR-A1-mediated phagocytosis of LPS/HMGB1/NETs and maintains gut microbial homeostasis, providing a potential therapeutic strategy for CIPN.
Project description:Marine brown algae produce the highly recalcitrant polysaccharide fucoidan, contributing to long-term oceanic carbon storage and climate regulation. Fucoidan is degraded by specialized heterotrophic bacteria, which promote ecosystem function and global carbon turnover using largely uncharacterized mechanisms. Here, we isolate and study two Planctomycetota strains from the microbiome associated with the alga Fucus spiralis, which grow efficiently on chemically diverse fucoidans. One of the strains appears to internalize the polymer, while the other strain degrades it extracellularly. Multi-omic approaches show that fucoidan breakdown is mediated by the expression of divergent polysaccharide utilization loci, and endo-fucanases of family GH168 are strongly upregulated during fucoidan digestion. Enzymatic assays and structural biology studies reveal how GH168 endo-fucanases degrade various fucoidan cores from brown algae, assisted by auxiliary hydrolytic enzymes. Overall, our results provide insights into fucoidan processing mechanisms in macroalgal-associated bacteria.
Project description:To investigate the fucoidan-induced global alteration of signalling pathways, we prepared bone marrow-derived dendritic cells (BMDCs) and treated them with fucoidan. We then performed gene expression profiling analysis using RNA-seq data from 6 different cells at one time point.
Project description:We present a study combining gene expression analyses and bioinformatic assessment. 1120 sequences annotated as sulfatase encoding from eight Rhodopirellula strains were clustered into 173 groups of orthologous and paralogous genes. A selection of 709 sulfatase gene strains were aligned to 66 sulfatase genes of known function to check for their respective substrate specificity. Thereby, 22 major phylogenetic clusters were observed with just five being mixed clusters between Rhodopirellula and reference sequences. This indicates a huge diversity on the substrate recognition level, unexpected from conventional annotations in public databases. Exemplarily, Rhodopirellula baltica SH1T was grown on different sulfated polysaccharides. Subsequent gene expression analyses using whole genome microarrays revealed distinct sulfatase expression profiles based on substrates tested. Expression profiles strongly point towards a functional link between sulfated polysaccharides and sulfatases. Moreover, further potential functions can be deduced from the expression profiles. In silico assessment backed up in vivo findings and raised the question, whether related strains and species are even more adapted to utilizing sulfated polysaccharides present in marine environments. Dual channel microarrays have been used for comparing the gene expression of R. baltica SH1T under reference condition (grown on glucose) and grown on sulfated polysaccharides as substrates of interest. Substrates tested have been: Chondroitin sulfate, lambda carrageenan and fucoidan. Control: 3 Biological replicates, Substrates tested: 2-3 Biological replicates, 2-3 replicates per array
Project description:Reactive oxygen species (ROS) produced during intracellular metabolism or triggered by extrinsic factors can promote neoplastic transformation and malignant microenvironment that mediate tumor development. Oligo-Fucoidan is a sulfated polysaccharide isolated from the brown seaweed. Using human THP-1 monocytes and murine Raw264.7 macrophages as well as human HCT116 colorectal cancer cells, primary C6P2-L1 colorectal cancer cells and human MDA-MB231 breast cancer cells, we investigated the effect of Oligo-Fucoidan on inhibiting M2 macrophage differentiation and its therapeutic potential as a supplement in chemotherapy and tumor prevention. We now demonstrate that Oligo-Fucoidan is an antioxidant that suppresses intracellular ROS and mitochondrial superoxide levels in monocytes/macrophages and in aggressive cancer cells. Comparable to ROS inhibitors (DPI and NAC), Oligo-Fucoidan directly induced monocyte polarization toward M1-like macrophages and repolarized M2 macrophages into M1 phenotypes. DPI and Oligo-Fucoidan also cooperatively prevented M2 macrophage invasiveness. Indirectly, M1 polarity was advanced particularly when DPI suppressed ROS generation and supplemented with Oligo-Fucoidan in the cancer cells. Moreover, cisplatin chemoagent polarized monocytes and M0 macrophages toward M2-like phenotypes and Oligo-Fucoidan supplementation reduced these side effects. Furthermore, Oligo-Fucoidan promoted cytotoxicity of cisplatin and antagonized cisplatin effect on cancer cells to prevent M2 macrophage differentiation. More importantly, Oligo-Fucoidan inhibited tumor progression and M2 macrophage infiltration in tumor microenvironment, thus increasing of anti-tumor immunity.