Abstract
Carrageenans are sulfated galactans found in certain red seaweeds with proven biological activities. In this work, we have prepared purified native and degraded κ-, ι-; and λ-carrageenans, including the disaccharides (carrabioses) and disaccharide-alditols (carrabiitols) from seaweed extracts as potential antitumor compounds and identified the active principle of the cytotoxic and potential antitumor properties of these compounds. Both κ and ι-carrageenan, as well as carrageenan oligosaccharides showed cytotoxic effect over LM2 tumor cells. Characterized disaccharides (carrabioses) and the reduced product carrabiitols, were also tested. Only carrabioses were cytotoxic, and among them, κ-carrabiose was the most effective, showing high cytotoxic properties, killing the cells through an apoptotic pathway. In addition, the cells surviving treatment with κ-carrabiose, showed a decreased metastatic ability in vitro, together with a decreased cell-cell and cell-matrix interactions, thus suggesting possible antitumor potential. Overall, our results indicate that most cytotoxic compounds derived from carrageenans have lower molecular weights and sulfate content. Potential applications of the results emerging from the present work include the use of disaccharide units such as carrabioses coupled to antineoplasics in order to improve its cytotoxicity and antimetastatic properties, and the use of ι-carrageenan as adjuvant or carrier in anticancer treatments.
Highlights
IntroductionRed seaweeds have been an important source of hydrocolloids (i.e. carrageenans and agarans), widely used both in food and non-food industries[1]
Red seaweeds have been an important source of hydrocolloids, widely used both in food and non-food industries[1]
The highest concentration employed, that is 0.1 mg/ml, was not considered in the analysis since the cytotoxic effect, which is clearly observed in the Figure, does not allow us to evaluate the migratory ability. In this novel study of carrageenans and their derived oligosaccharides, we found that the presence of sulfate groups is a factor abrogating its potential cytotoxicity of native carrageenans, being the κ- and ι-carrageenans the more active agents among the polysaccharides
Summary
Red seaweeds have been an important source of hydrocolloids (i.e. carrageenans and agarans), widely used both in food and non-food industries[1]. These carrageenans are attractive due to their rheological properties as stabilizers and thickening or gelling agents[2] Both κ- and ι-carrageenans can form gels upon cooling or in the presence of K+ or Ca2+ counterions[3], whereas λ-carrageenan hardly gels, or needs high concentrations of K+ to give weak gels[4,5]. They can be used in the food, pharmaceutical, cosmetics, printing and textile industries It was reported their use as renewable, ecological and nontoxic mobility control agents to increase sweep efficiency for oil recovery in dwindling petroleum reserves[7]. Besides their commercial interest, carrageenans are known to have biological properties as well as low toxicity. GAG portion of the proteoglycans and the extracellular matrix proteins, eliminating the adhesion of cancer cells to matrices, which is necessary in metastasis spread[11]
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