Oligo-Fucoidan prevents IL-6 and CCL2 production and cooperates with p53 to suppress ATM signaling and tumor progression

Tseng

et al. 2020

Cancers

Self Cite

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.

Section: Cisplatin and Oligo-fucoidan Additively Enhance Cancer Cell mentioning

confidence: 72%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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Oligo-Fucoidan Prevents M2 Macrophage Differentiation and HCT116 Tumor Progression

Tseng

et al. 2020

Cancers

Self Cite

J Neurol Surg B Skull Base

“…Its main role is to regulate immune and inflammatory responses and regulate the proliferation and differentiation of tumor cells. 18 IL-6, an immunomodulatory cytokine, has been extensively studied in the field of cancer, and it initiates different signaling pathways leading to tumor proliferation, angiogenesis, and drug resistance. Previous studies showed that IL-6 can initiate EMT processes and promote the migration and metastasis of squamous cell carcinoma of the head and neck through activating the downstream PI3-K/Akt/mTOR and MAPK/ERK signaling pathways by upregulating p70S6K.…”

Section: Discussionmentioning

confidence: 99%

Correlation between the Expression of Interleukin-6, STAT3, E-Cadherin and N-Cadherin Protein and Invasiveness in Nonfunctional Pituitary Adenomas

Shen

Liu

et al. 2019

Objective This study aimed to investigate the expression of interleukin (IL)-6, signal transducer and activator of transcription 3 (STAT3), epithelial-cadherin (E- cadherin) and neural-cadherin (N-cadherin) proteins in nonfunctional pituitary adenomas, and their correlation with invasiveness. Method Thirty cases of nonfunctional pituitary adenoma pathological wax specimens were selected from our hospital, including 20 cases of invasive nonfunctional pituitary adenoma (INFPA) and 10 noninvasive nonfunctional pituitary adenomas (NNFPAs). Envision was used to detect IL-6, STAT3, E-cadherin , and N-cadherin in specimens. Statistical methods were used to analyze the correlation between the four proteins and the Knosp classification of nonfunctional pituitary adenomas. Result IL-6 and STAT3 were highly expressed in INFPAs but poorly expressed in NNFPAs. E-cadherin expression in INFPAs was lower than that in NNFPAs. N-cadherin was positive or strongly positive in both groups. Spearman's correlation analysis showed that the expression of IL-6 and STAT3 was positively correlated with Knosp's classification, whereas the expression of E-cadherin was negatively correlated with Knosp classification. Meanwhile, the expression of N-cadherin was not correlated with Knosp's classification. Conclusion The expression of the IL-6, STAT3, E-cadherin proteins were associated nonfunctional pituitary adenomas. However, the expression of N-cadherin was not correlated with nonfunctional pituitary adenomas.

“…All these studies tried to investigate fucoidans molecular mechanisms in relation to their chemical structure and physicochemical properties. Therefore, different hypotheses were suggested for each activity, such as anti-tumor [31,[38][39][40], anti-coagulant [41,42], anti-viral [43,44] and anti-inflammatory activity [45,46]. These investigations revealed that various factors are relevant, such as molecular weight, sulfation pattern, sulfate content and monomeric composition [47][48][49].…”

mentioning

confidence: 99%

Fucoidans: Downstream Processes and Recent Applications

Zayed

Ulber

2020

Marine Drugs

Fucoidans are multifunctional marine macromolecules that are subjected to numerous and various downstream processes during their production. These processes were considered the most important abiotic factors affecting fucoidan chemical skeletons, quality, physicochemical properties, biological properties and industrial applications. Since a universal protocol for fucoidans production has not been established yet, all the currently used processes were presented and justified. The current article complements our previous articles in the fucoidans field, provides an updated overview regarding the different downstream processes, including pre-treatment, extraction, purification and enzymatic modification processes, and shows the recent non-traditional applications of fucoidans in relation to their characters. of 22reproductive, immune and cell-to-cell communicative roles [23]. As recommended by the International Union of Pure and Applied Chemistry (IUPAC), fucoidans is a general term used to describe sulfated L-fucose-based polymers including sulfated fucans cited by the Swedish scholar Kylin, as well as other fucose-rich sulfated heteropolysaccharides [23,28]. Their chemical structures, in terms of monomeric composition and branching, are quite simple in marine invertebrates compared to their analogues in brown algae [13,29].Hundreds of articles have thoroughly discussed and reviewed the biological, pharmacological and pharmaceutical applications of fucoidans [30][31][32][33], including nanomedicine, [34] which has made it a hot topic in the last few decades [35][36][37]. All these studies tried to investigate fucoidans molecular mechanisms in relation to their chemical structure and physicochemical properties. Therefore, different hypotheses were suggested for each activity, such as anti-tumor [31,[38][39][40], anti-coagulant [41,42], anti-viral [43,44] and anti-inflammatory activity [45,46]. These investigations revealed that various factors are relevant, such as molecular weight, sulfation pattern, sulfate content and monomeric composition [47][48][49]. For example, different fractions were produced with different physicochemical properties in our previous experiments; sulfation pattern and sulfate content were highly related to anti-viral and cytotoxic activities against HSV-1 and Caco-2 cell lines, respectively, while molecular weight and sugar composition were potential factors in anti-coagulation activity [41,50]. In addition, degree of purity was reported as an influential factor [32], where co-extracted contaminants (e.g., phlorotannins or polyphenols) could lead to significant interference in anti-oxidant activity and, consequently, cosmetic applications [51,52].Therefore, several key production challenges regarding fucoidans were discussed in our last review article in order to obtain a product that follows the universal good manufactured practice (GMP) guidelines. The article discussed sources of heterogeneity in extracted fucoidans, including the different biotic (e.g., biogenic, geographical and seas...