Ultrasound-assisted fast preparation of low molecular weight fucosylated chondroitin sulfate with antitumor activity

Abstract Fucosylated chondroitin sulfate from sea cucumber Isostichopus badionotus (fCS- Ib ) was depolymerized with an ultrasound-accelerated, metal-free Fenton chemistry, relying on H 2 O 2 /ascorbic acid redox system. Fragments of different molecular weights were obtained at different reaction temperatures, ascorbic acid concentrations and ultrasonic intensities. The structures of two typical depolymerized fragments were evaluated using high-performance liquid chromatography (HPLC), infrared spectroscopy (IR), and nuclear magnetic resonance spectroscopy (NMR). The results showed that ultrasound enhanced the degradation efficiency of H 2 O 2 /ascorbic acid system mainly by disaggregating sulfated polysaccharide clusters and that free radicals induced depolymerization with no significant chemical changes in the backbone of fCS- Ib and with no obvious loss of fucose branches. The antitumor activity, using A549 lung cancer cells, showed that the ultrasound treated low molecular weight sulfated fragment enhanced proliferation-inhibitory and anti-migration effects, compared to native fCS- Ib . This was different from the anticoagulant activity of fCS- Ib , suggesting that the molecular weight change may cause a conformational transition and affect biological activity. We propose that combining ultrasound with non-metal Fenton chemistry as an effective method to prepare low molecular weight fCS fragments with potential applications as functional foods, antitumor drugs, and that these fCS fragments display negligible bleeding risk.