Fucoidan as an Autophagy Regulator: Mechanisms and Therapeutic Potentials for Cancer and Other Diseases.

Fucoidan, a natural polysaccharide with a variety of classical bioactivities mainly sourced from brown algae, has been extensively studied owing to its favorable pharmacological effects, including anti-inflammatory, anti-tumor, anticoagulant and liver protection. Recently it has been found to play a regulatory role in the processes of autophagy. Autophagy is an important cellular process that effectively protects cells and organisms from stimulating factors such as nutrient deficiency, low cellular ATP levels, metabolic stress, growth factor deprivation and hypoxic conditions. In recent years, many studies have shown that fucoidan can treat human diseases by regulating autophagy process though cell signaling pathways. In this review, we summarize the latest progress in the discovery of natural autophagy regulator of fucoidan for the therapeutic application in cardiac diseases, cancers and liver diseases, aiming to provide the new pharmacological application that fucoidan may treat human diseases by regulating autophagy. Furthermore, we look forward to seeing more diseases that would be treated by autophagy modulator of fucoidan and the discovery of more elaborate autophagy regulation mechanism.

Inhibition of fucoidan on breast cancer cells and potential enhancement of their sensitivity to chemotherapy by regulating autophagy.

Fucoidan is a marine-origin sulfated polysaccharide that has gained attention for its anticancer activities. However, the inhibitory effect of fucoidan on breast cancers by regulating autophagy and its mechanism are not clear, and the chemotherapeutic sensitization of fucoidan is largely unknown. In the present study, the anticancer potential of fucoidan was revealed in MCF-7 and MDA-MB-231 cells. Additionally, we also studied the chemotherapeutic sensitization of fucoidan by combining chemotherapeutic drugs doxorubicin (ADM) and cisplatin (DDP) with fucoidan on breast cancer cells. In the two kinds of human breast cancer cells, cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptosis was examined with flow cytometry. Transfection assay was used to examine autophagy flow. Western blot was used to examine the expressions of related proteins. Results suggested that fucoidan could induce autophagy and might enhance the sensitivity of breast cancer cells to chemotherapeutic drugs. Mechanistically, fucoidan induced autophagy in breast cancer cells by down-regulating m-TOR/p70S6K/TFEB pathway. In conclusion, our research revealed that fucoidan could induce autophagy of breast cancer cells by mediating m-TOR/p70S6K/TFEB pathway, thus inhibiting tumor development. Furthermore, fucoidan might enhance the sensitivity of breast cancer cells to ADM and DDP, and this enhancement was related to autophagy.

Metabolic regulation mechanism of fucoidan via intestinal microecology in diseases.

The intestinal microecology is an extremely complex ecosystem consisting of gut microbiota, intestinal mucosa and the intestinal immune system. The intestinal microecology performs several important functions and is considered to be an essential 'organ' because it plays an important role in regulating human metabolism. Fucoidan contains a large amount of fucose and galactose residues, as well as various other neutral and acidic monosaccharides. Fucoidan particularly effects tumors, inflammatory bowel disease, diabetes and obesity by repairing intestinal mucosal damage and improving the intestinal microecological environment. It has been proposed that fucoidan could be used as a prebiotic agent for pharmaceutical and functional foods. In this review, we elucidate the potential mechanisms of the metabolic regulation of fucoidan with respect to the intestinal microecology of diseases. © 2021 Society of Chemical Industry.