A review on fucoidan antitumor strategies: From a biological active agent to a structural component of fucoidan-based systems
Introduction
More than 70 % of the world’s surface is covered by oceans, being plants, animals, and microorganisms from the marine environment a significant source of natural products (Penesyan, Kjelleberg, & Egan, 2010). Among marine organisms, marine algae are rich sources of structurally diverse bioactive compounds with relevant biological activities (Khalid, Abbas, & Saeed, 2018). Marine algae are a good source of nutrients, being of particular interest their sulfated polysaccharides (Silva et al., 2012). The growing interest in marine polysaccharides extracted from brown algae is due to their therapeutic effects against different types of disorders and pathological conditions. In addition, the greater availability and lower production costs are other advantages of these algae polysaccharides, enabling their use at industrial scale (Khan, Shin, & Kim, 2018). Indeed, seaweeds have been exploited as supplements in functional food or the extracted compounds used in the development of new pharmaceutical agents and medical oriented products (Khalid et al., 2018). In this regard, the biomedical market represents an enormous opportunity for many of these bioactive compounds and materials. The exploitation of natural resources may present a potential added value that justify the potential risks related with the development and approval of such products (Silva et al., 2012).
Fucoidans are a class of sulfated polysaccharides, mainly composed by fucose, that can be extracted from different species of brown algae (Cunha & Grenha, 2016). Fucoidans are already available as food/dietary supplements and in cosmetics. However, they are not yet approved for biomedical applications, neither by direct administration nor by its incorporation in biomaterials, despite showing promising outcomes (Fitton, Stringer, & Karpiniec, 2015; Wells et al., 2017). In fact, fucoidan has been described to present distinct biological activities, namely antitumor, anti-viral and anti-inflammatory, as well as immunoregulatory and (anti-)angiogenic potential (Li, Lu, Wei, & Zhao, 2008; Wang, Kankala et al., 2019; Wang, Xing et al., 2019). Despite these achievements, variable and contradictory results compromise fucoidan usage in the clinic (Atashrazm, Lowenthal, Woods, Holloway, & Dickinson, 2015). The huge variety of algae fucoidan sources, allied to various extraction and purification methods, may influence fucoidan’s physicochemical properties and bioactivity (Cunha & Grenha, 2016; Fitton et al., 2015) (Fig. 1).
In this review, a general introduction to fucoidan composition, chemical structure and physicochemical properties is addressed. The recent advances of fucoidan as an antitumor bioactive agent, divided by different types of cancer (i.e. colon, lung, breast and melanoma) is reviewed. In addition, the development and biological outcomes of fucoidan-based systems (mainly nanoparticles) is addressed in detail.
Section snippets
Fucoidan composition and chemical structure
Fucoidan may be extracted from different seaweed species, presenting different chemical compositions. In general, fucoidans from brown algae present a backbone of α(1 → 3) l-fucopyranose residues or of alternating α(1 → 3) and α(1 → 4)-linked l-fucopyranosyls, that can be replaced by sulfate or acetate and/or have side branches containing fucopyranoses or other glycosyl units, e.g. glucuronic acid. Fucoidan structures may also be composed of other monosaccharides as glucose, xylose, galactose
Fucoidan physicochemical properties
As previously stated, the extraction conditions, algae species and life cycle state, among others, have a huge influence over fucoidan composition and chemical structure, providing extracts with different molecular weights and sulfate patterns (Mak, Hamid, Liu, Lu, & White, 2013). The molecular weight is one of the main properties described to influence the biological activity of fucoidans. Nevertheless, it is difficult to establish a direct correlation based in one property alone (
Anti-cancer activity
Cancer is characterized by an uncontrolled cell growth and can start at any tissue of the body. Cancer cells can spread to tissues other than where they started proliferating, causing metastasis (Cooper, 2000). Although more people than ever have survived different types of cancer after treatment, cancer is still one of the main causes of death worldwide (Siegel, Miller, & Jemal, 2019). The type of cancer, size and location will influence the treatment options which may include chemotherapy,
Fucoidan-based systems for anti-cancer therapies
Most of the studies that explore the potential use of fucoidan to treat different types of cancer use fucoidan in its soluble form. However, in recent years, fucoidan-based systems have been developed aiming to develop more effective anti-cancer strategies. Most of them are nanosystems that comprise the use of nanoparticles (NPs), micelles or liposomes, playing an important role in biological systems (Chollet et al., 2016). Indeed, fucoidan has been included in nanosystems for diagnostic, drug
Conclusion and future perspectives
In this review, a brief description of fucoidan structure and physicochemical properties that make it a promising and versatile polysaccharide are explained. Despite the enthusiastic results, and the fact that fucoidan products have been commercialized as dietary or nutritional supplements for different diseases, including cancer, the use of fucoidan in the clinic has not been approved so far. Some contradictory results regarding its biological outcomes may be one of the possible reasons.
Acknowledgments
This work was developed under the scope of the Structured projects for R&D&I NORTE-01-0145-FEDER-000021 and NORTE-01-0145-FEDER-000023 supported by the Northern Portugal Regional Operational Programme (NORTE 2020), and the Mobilizing Project ValorMar, POCI-01-0247-FEDER-024517, supported by the Operational Programme for Competitiveness and Internationalization (COMPETE 2020), under the Portugal 2020 Partnership Agreement, co-funded by European Regional Development Fund (ERDF). The authors would
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