In the field of pharmacology, the biologically active polysaccharides (PSs) that are derived from natural sources have attained a special place for the development of drug lead molecules. Marine macroalgae contain a significant amount of soluble PSs and have potential function as dietary fiber. Specially, brown marine algae are known to produce functional PSs such as alginates and fucoidans. Seaweed-derived PSs have been
reported to exhibit biological activities like anticoagulant, anti-inflammatory, antiviral, and antitumoral activities (Costa et al., 2010). Among the various PSs found in seaweeds, fucoidans, carragenan, and ulvan (Fig. 16.1) have been studied for their potential role in controlling cancer.
Fucoidan, an ingredient of marine algae, is composed of a polymer of a1 ! 3-linked l-fucose, with sulfate groups on some of the fucose residues at four positions (Patankar et al., 1993). Out of the many biologically effective activities of fucoidans, in vitro and in vivo studies have reported that marine algae fucoidans possess antitumor, anticancer, antimetastatic, and fibrinolytic properties in mice (Religa et al., 2000). In one of the in vitro studies, fucoidan isolated from Laminaria guryanovae has effectively inhibited the neoplastic cell transformation by inhibiting the phosphorylation of epidermal growth factor receptor (EGFR) in mouse epidermal JB6 Cl41 cells (Lee et al., 2008). As it is evident that EGFR, one of the receptor tyrosine kinases, plays a pivotal role in regulating cell proliferation, differentiation, and transformation and is also considered as a target for the treatment of cancers, the inhibitory activity of fucoidan suggests that marine edible algae could possibly reduce the risk of cancers when considered as dietary supplements. In Asian countries such as China, Japan, and Korea, seaweeds are considered as dietary supplements and also are reported to have been used for boosting up the immune system. Mekabu (sporophyll of Undaria pinnatifida), a dietary alga, is reported to exert antitumor activity and enhance the immune response. In vivo studies of effect of fucoidans isolated from Mekabu are reported to reduce the tumor growth. The experimental mice (T cell receptor transgenic (DO11.10—Tg)) were fed with a diet containing 1% Mekabu fucoidan, and it was reported that mice that were fed with the Mekabu fucoidan had a reduction on tumors by 65.4%. This in vivo study also reports that Mekabu fucoidan mediates tumor destruction through T-helper (Th1) cell and natural killer (NK) cell responses (Maruyama et al., 2006). These findings clearly suggest the efficacy of marine algal fucoidans for the possible application in the treatment of tumors and cancers.
The antitumor and antimetastatic activities of fucoidan from Fucus evanescens have been studied in vivo in C57Bl/6 mice with transplanted Lewis lung adenocarcinoma. It was observed that single and repeated administration of fucoidan in dose of 10 mg/kg has exhibited moderate antitumor and antimetastatic effects and potentiated the antimetastatic, but not antitumor, activities of cyclophosphamide (Li et al., 2008).
The linear form of SPs and carrageenans extracted from red algae has been reported to have many applications in the food industry as well as in the medicinal industry. Carrageenans, a family of SPs isolated from marine red algae, are widely used as food additives, such as emulsifiers, stabilizers, or thickeners (Campo et al., 2009). Out of the various forms of carrageenans from red algae, l-carrageenan is a sulfated galactan isolated from some red algae and has been reported to have many kinds of biological activities. One of the research groups has isolated l-carra-geenan with different molecular weights 650, 240, 140, 15, and 9.3 kDa from a Chinese red algae Chondrus ocellatus to study their tumor-inhibiting activities. Their research investigation on l-carrageenan-treated mice of transplanted S180 and H22 tumor has shown considerable antitumor and immunomodulation activities in different degrees. It is although reported that molecular weight of this PS has notable antitumor and immunomodulation activities by means of activating the immunocompe-tence of the body (Zhou et al., 2004). The antioxidant and antitumor activities of marine algal extracts are becoming popular in current days' research. Hot-water-soluble PS of the marine alga Capsosiphon fulvescens have been reported to exhibit inhibition activities on cultured human cancer cells in a dose-dependent manner in vitro. The detailed mechanistic studies at molecular level have revealed that the cancer inhibitory effect of these hot-water-soluble PSs was in correlation with an increase in cas-pase-3 activation and a decrease in Bcl-2 expression, thus inducing apo-ptosis by inhibiting IGF-IR signaling and the PI3K/Akt pathway (Kwon and Nam, 2007). The carrageenan's low cytotoxic effects and their immunomodulation and antitumor activities should be considered and can be recommended for the anticancer therapies that can give a breakthrough for the proper management of cancer-related therapies.
Ulvans are structural acid PSs present in cell wall of green algae (Ulva and Enteromorpha). They are highly sulfated and essentially composed of rhamnose 3-sulfate, xylose, xylose 2-sulfate, glucuronic acid, and iduronic acid units. Ulvan displays several physiochemical and biological features of potential interest for food, pharmaceutical, agricultural, and chemical applications (Lahaye and Robic, 2007). Formation of free radicals due to the oxidative stress is thought to be a major contributor for the formation of cancer cells in the human body. Several research groups have suggested that low molecular weight SPs have shown potent antioxidant activity than high molecular weight SPs. For instance, different molecular weight ulvans from Ulva pertusua (Chlorophyceae) were investigated for H2O2 degradation and their antioxidant activities. Their results showed that low molecular weight ulvans have a strong antioxidant activity. The rationale for this is low molecular weight SPs may incorporate into the cells more efficiently and donate proton effectively compared to high molecular weight SPs (Qi et al., 2005). This antioxidation ability of the ulvans can be exploited for the preparation of medicinal compounds that can control the progress of cancer. On the other hand, in vitro and in vivo antitumor properties of an SP isolated from the marine algae Champia feldmannii (Cf-PLS) have revealed that inhibition rates of sarcoma 180 tumor development were 48.62% and 48.16% at the doses of 10 and 25 mg/kg, respectively, which clearly suggest the efficacy of marine algal PSs as potential antitumor agents (Lins et al., 2009). Importantly, SPs from marine algae are known to be important free-radical scavengers and antioxidants for the prevention of oxidative damage, which is an important contributor in carcinogenesis. Therefore, it might be suggested that these seaweed-derived SPs have potent capacities for new anticancer product developments in the pharmaceutical as well as in the food industries as novel chemo-preventing agents for cancer therapy (Wijesekara et al., 2011). Moreover, the marine macroalgae are considered as dietary constituents and are rich in SPs like fucoidans, carrageenan, and ulvan and thus can be recommended as medicinal foods to reduce the incidence of cancers.
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