Abstract
The fucoidan with high anticancer activity was isolated from brown alga Fucus evanescens. The compound effectively prevented EGF-induced neoplastic cell transformation through inhibition of TOPK/ERK1/2/MSK 1 signaling axis. In vitro studies showed that the fucoidan attenuated mitogen-activated protein kinases downstream signaling in a colon cancer cells with different expression level of TOPK, resulting in growth inhibition. The fucoidan exerts its effects by directly interacting with TOPK kinase in vitro and ex vivo and inhibits its kinase activity. In xenograft animal model, oral administration of the fucoidan suppressed HCT 116 colon tumor growth. The phosphorylation of TOPK downstream signaling molecules in tumor tissues was also inhibited by the fucoidan. Taken together, our findings support the cancer preventive efficacy of the fucoidan through its targeting of TOPK for the prevention of neoplastic cell transformation and progression of colon carcinomas in vitro and ex vivo.
Highlights
Cancer is considered to be a leading cause of death worldwide despite the intensive efforts and substantial advances that have occurred through focusing on improving treatments
We investigated whether the fucoidan might influence kinase activity of T-cell-originated protein kinase (TOPK) for the inhibition of cells transformation
The fucoidans isolated from different species of brown algae have extremely diverse chemical structure
Summary
Cancer is considered to be a leading cause of death worldwide despite the intensive efforts and substantial advances that have occurred through focusing on improving treatments. Chemoprevention may be defined as the use of non-toxic substances, including many food factors and natural compounds to interfere with the process of cancer development or carcinogenesis before invasion and metastasis can occur. On the basis of this idea, and numerous epidemiological findings, attention has centred on dietary natural compounds as an effective intervention in cancer development [1]. A great deal of interest has been developed in the nutraceutical and pharmaceutical industries to isolate natural biological active compounds from marine resources. Brown algae are known to produce a range of active components including unique secondary metabolites such as phlorotannins and polysaccharides, namely alginic acids, laminarans, and sulfated polysaccharides (fucoidans). The fucoidans are shown to be a topic of numerous studies as nontoxic compounds, possessing wide spectrum of biological activities [3, 4]. The fucoidans from different species of brown algae have been found to inhibit carcinogenesis in variety of cancer cells, including gastric adenocarcinoma [5], prostate cancer [6], melanoma [7], hepatocellular carcinoma [8], breast cancer [9], and colon cancer cells [10]
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