We have found that the low-molecular Fucoidan (LMF), high-molecular weight Fucoidan (HMF) and other Fucoidan derivatives from have different protective effects against ultraviolet B (UVB) damage on skin cells28. phosphorylation in p53+/+ cells compared with p53?/? cells. Similarly, co-administration of Oligo-Fucoidan with etoposide inhibits ATM, Chk1 and -H2AX phosphorylation, particularly in the presence of p53. Furthermore, Oligo-Fucoidan supplementation increases cancer cell death and attenuates the adverse effects induced by etoposide that decreases production of the pro-inflammatory cytokine IL-6 and chemokine CCL2/MCP-1. Importantly, Oligo-Fucoidan decreases the tumor-promoting M2 macrophages in microenvironment as well as collaborates with p53 and works in combination with etoposide to prevent HCT116 tumorigenicity. Our results first demonstrate that p53 enables Oligo-Fucoidan to effectively inhibit tumor progression, and Oligo-Fucoidan minimizes the side effects of chemotherapy and alters tumor microenvironment. Introduction Seaweeds contain many bioactive components of polysaccharides and polyphenols1, which exhibit therapeutic potential such as anti-cancer, anti-oxidant, anti-inflammatory and anti-diabetic effects2. Fucoidan is a sulfated fucose-rich polysaccharide isolated from brown seaweed and is under consideration for use as a functional food that can prevent disease and improve health3C5. In addition to exerting anti-oxidant6 and anti-inflammatory effects7, Fucoidan also increases cancer cell apoptosis8,9 and induces cell cycle arrest10,11. Angiogenesis promotes tumor progression and metastasis12. Fucoidan treatment suppresses angiogenic activity by inhibiting vascular endothelial growth factor (VEGF) receptor expression and VEGF-induced human umbilical vein endothelial cell proliferation13,14. Matrix metalloproteinases (MMPs) and nuclear factor-kappa B (NF-B), which regulate VEGF expression and hypoxia-inducible factor 1-alpha/VEGF signaling under hypoxic conditions, are also inhibited by Fucoidan treatment, which may prevent metastasis in tumor-bearing mice15,16. Tumor microenvironment (TME) mediates tumor aggressiveness17. Fucoidan has anti-inflammatory effects that suppress nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and monocyte chemoattractant protein-1 (MCP-1/CCL2) expression, as well as pro-inflammatory cytokine production, namely, interleukin-1 (IL-1) and tumor necrosis factor (TNF)- production7,18. Moreover, Fucoidan has been shown to have immune-modulatory results by improving organic killer (NK) cell and cytotoxic T-cell (CTL) amounts and activity19C21. A earlier study demonstrated that CTLs screen higher cytotoxicity against tumor cells when co-cultured with Fucoidan-treated dendritic cells (DCs) than when cultured only22. However, another scholarly research demonstrated that Fucoidan induces manifestation from the anti-apoptotic protein Mcl-1, inactivates caspase-3 and activates SULF1 the phosphoinositide 3-kinase/AKT signaling pathway to inhibit neutrophil apoptosis23. As an antioxidant, Fucoidan protects cells against oxidative tension by scavenging superoxide radicals24; inducing manifestation from the anti-oxidant nuclear element erythroid-2-related element 2 which of its focus on gene, superoxide dismutase25; and suppressing the changing growth element (TGF-)/Smad pathway26, which prevents reactive oxidative varieties (ROS) era in tumor cells and ROS launch in to the TME27. These total results claim that Fucoidan modifies the TME. The space of sugars backbone string and the quantity of sulfate organizations affect the natural activity of Fucoidans. We’ve discovered that the low-molecular Fucoidan (LMF), high-molecular pounds Fucoidan (HMF) and additional Fucoidan derivatives from possess different protective results against ultraviolet B (UVB) harm on pores and skin cells28. In comparison with HMF, LMF even more protects your skin cells against UVB harm and Antitumor agent-2 lowers collagen degradation by avoiding the activation of transcription element activator protein-1 (AP-1) which induces collagenases (MMP-1, MMP-8 and MMP-13) and gelatinase (MMP-9) but suppresses TGFRII Antitumor agent-2 manifestation under UVB harm. Previous research also indicated that LMF promotes TGF- receptor degradation and induces Toll-like receptor 4-controlled reactive oxygen varieties that promotes endoplasmic reticulum stress-mediated apoptosis in lung tumor cells, inhibiting lung tumor development29 therefore,30. It really is unclear to day whether low-molecular-weight Fucoidan (LMF) (also called Oligo-Fucoidan) cooperates with tumor suppressor to help expand prevent tumor development and modification tumor microenvironment. Right here, we first proven that Oligo-Fucoidan collaborates with p53 to avoid spontaneous or etoposide-induced DNA breaks also to regulate the DNA harm response and cell routine checkpoint. Furthermore to efficiently reducing the comparative unwanted effects and improving the restorative outcomes of etoposide, Oligo-Fucoidan also avoided tumor advancement in mice bearing HCT116 human being cancer of the colon cells and suppressed M2 macrophage polarization. These total outcomes indicate that Oligo-Fucoidan can be a guaranteeing health supplement with regards to the treatment of tumor, as the substance enhances tumor suppressor activity, modulates cytokine profiles and alters tumor microenvironment. Outcomes Oligo-Fucoidan and p53 prevent spontaneous DNA breaks in HCT116 tumor cells Two isogenic HCT116 colorectal tumor cell lines without (p53?/?) or with (p53+/+) regular p53 expression had been used to compare and contrast the consequences of monotherapy with those of simultaneous or sequential mixture therapy. When the p53?/? as well as the p53+/+ cells had been treated with different concentrations of Oligo-Fucoidan for 48?h (Fig.?1a), the phosphorylation (Ser139) of Histone H2AX (-H2AX), a biomarker for DNA double-strand Antitumor agent-2 breaks (DSBs), decreased significantly inside a dose-dependent way particularly in the p53+/+ cells. Oligo-Fucoidan also suppressed p53 (Ser15) phosphorylation and p21 manifestation. These results imply Oligo-Fucoidan protects the cells.