In vitro cancer chemopreventive properties of polysaccharide extract from the brown alga, Sargassum latifolium

Abstract

Polysaccharides of edible algae attracted extensive interest due to their numerous biological activities. Sargassum latifolium (Turner) C. Agardh, belongs to Sargassaceae, is a brown algae in red sea shores in Egypt. This work is a novel attempt to explore the cancer chemopreventive activity of different fractions of water-soluble polysaccharide extract derived from S. latifolium. Estimation of cancer chemopreventive activity, specifically anti-initiation, including the modulation of carcinogen metabolism and the antioxidant capacity, revealed that E1 and E4 were potent anti-initiators, where they lead not only to an inhibition in the carcinogen activator cytochrome P450 1A (IC50 2.54 and 10.30 μg/ml, respectively), but also to an induction in the carcinogen detoxification enzymes glutathione-S-transferases (144% and 225% of the control, respectively). E1 and E4 inhibited 59% and 63% of the induced-DNA damage, as measured by comet assay. Similarly both E1 and E4 possessed potential anti-promoting properties as indicated by their anti-inflammatory activity. E1 and E4 enhanced the macrophage proliferation; however they dramatically inhibited the stimulated NO (30.7% and 59.3%), TNF-α (38.2% and 54.9) and COX-2 (20% and 18%), respectively. E3 showed a selective cytotoxicity against lymphoblastic leukemia (1301 cells), while other fraction extracts had no cytotoxic effect against all tested cell lines. E3 led to a major disturbance in cell cycle including arrest in both S-phases in 1301 cells. This disturbance was associated with an induced-cell death due to apoptosis, but not necrosis. In conclusion, E1 and E4 are promising cancer chemopreventive fractions, since they had tumor anti- initiating activity via their protective modulation of carcinogen metabolism, and tumor anti-promoting activity via their anti-inflammatory activity, while E3 can be considered as a promising anti-cancer agent against leukemia.

Introduction

Brown algae contain large amounts of cell-wall polysaccharides, most of which are sulfated polysaccharide fucoidans (Asker et al., 2007). Algal polysaccharides attracted extensive interest to study their numerous biological activities. Recently, several investigations have been focused on the isolation and function of the polysaccharides derived from different Sargassum species, which revealed multiple biological activities such as hepatic and renal protective activity (Josephine et al., 2007, Raghavendran et al., 2007) and antioxidant (Jung et al., 2008, Zhou et al., 2008), anti-tumor, anti-angiogenic (Dias et al., 2005), anti-inflammatory (Chang et al., 2008), anti-coagulant (Athukorala et al., 2007), anti-viral (Zhu et al., 2006) and anti-vasculogenic (Dias et al., 2008) activities.

Generally, the biological activity of polysaccharides from marine algae is related to the molecular size, type of sugar, sulphate content, type of linkage and molecular geometry are also known to have a role in their activities (Zhu et al., 2004). Edible seaweeds have high nutritional values as sources of vitamins, minerals, and non-caloric dietary fibers and as potential sources of biological active ingredients (Yan et al., 1999). Sargassum latifolium (Turner) C. Agardh is one of the edible brown algae in red sea shores in Egypt and it also widely distributed in Japan and gulf area. S. latifolium belongs to class Phaeophyceae, order Fucales, family Sargassaceae. S. latifolium has Unambiguous Synonyms including Carpacanthus latifolius (Turner), and Fucus latifolius Turner. In a recent report, S. latifolium was found to have promising anti-viral activity (Asker et al., 2007).

During the cancer multi-stage cascade, normal cells undergo initiation, promotion, and progression processes. Extensive researches on the cellular and molecular basis of the carcinogenesis cascade provides a targeted approach for cancer chemoprevention, which aims to halt or reverse the development and progression of precancerous cells through use of non cytotoxic doses of nutrients and/or pharmacological agents (Theisen, 2001). Identification of novel effective cancer chemopreventive agents has become an essential worldwide strategy in cancer prevention. Finding of cancer chemopreventive activity could elevate seaweed (S. latifolium) value as a food or additive as expanding its market and uses in food industries. In this work, we extracted different fractions of water-soluble polysaccharide from S. latifolium and we investigated their cancer chemopreventive activity that might prevent different stages of carcinogenesis process.