Low-molecular-weight Fucoidan (Oligo-Fucoidan) is a sulfated polysaccharide that has a variety of biological effects and has also been shown to have beneficial health effects. However, the molecular mechanisms underlying the therapeutic effects of Oligo-Fucoidan in patients with cancer remain unclear. Using human colorectal cancer HCT116 cells with (p53^+/+) or without (p53^-/-) normal p53 expression, we found that Oligo-Fucoidan treatment reduces the occurrence of spontaneous DNA lesions. Etoposide induces double strand DNA breaks. Subsequent administration of Oligo-Fucoidan to etoposide-treated cells promotes p53 accumulation, p21 expression and significant decreases in ataxia-telangiectasia-mutated (ATM), checkpoint kinase 1 (Chk1) and γ-H2AX phosphorylation in p53^+/+ cells compared with p53^-/- cells. Similarly, co-administration of Oligo-Fucoidan with etoposide inhibits ATM, Chk1 and γ-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.

中文翻译：

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Oligo-Fucoidan可防止IL-6和CCL2的产生，并与p53协同抑制ATM信号传导和肿瘤进展。

低分子量岩藻依聚糖（Oligo-岩藻依聚糖）是一种硫酸化多糖，具有多种生物学作用，并且还显示出有益于健康的作用。然而，Oligo-岩藻依聚糖对癌症患者的治疗作用的分子机制仍不清楚。使用具有（p53 ^{+ / +}）或不具有（p53 ^-/-）正常p53表达的人大肠癌HCT116细胞，我们发现Oligo-Fucoidan处理可减少自发性DNA损伤的发生。依托泊苷诱导双链DNA断裂。随后向依托泊苷处理的细胞中施用寡糖-岩藻依聚糖可促进p53积累，p21表达，并使共济失调-毛细血管扩张突变（ATM），检查点激酶1（Chk1）和γ-H2AX磷酸化显着降低p53 ^{+ / +}与p53 ^-/-细胞相比。同样，寡糖-岩藻依聚糖与依托泊苷的共同给药会抑制ATM，Chk1和γ-H2AX磷酸化，特别是在存在p53的情况下。此外，寡聚岩藻依聚糖的补充增加了癌细胞的死亡并减轻了依托泊苷诱导的不良反应，这降低了促炎性细胞因子IL-6和趋化因子CCL2 / MCP-1的产生。重要的是，Oligo-Fucoidan减少了微环境中促进肿瘤的M2巨噬细胞，并与p53协同作用并与依托泊苷联用，以预防HCT116致瘤性。我们的结果首次证明，p53使Oligo-Fucoidan有效抑制肿瘤进展，而Oligo-Fucoidan可使化学疗法的副作用降至最低，并改变了肿瘤的微​​环境。