Degraded fucoidan fractions and β-1,3-glucan sulfates inhibit CXCL12-induced Erk1/2 activation and chemotaxis in Burkitt lymphoma cells.

Fucoidans are natural polysaccharides with pronounced antitumoral activities. Their modes of action include the antagonization of the chemokine CXCL12, which plays a central role in tumor development and metastasis. However, the usually high molecular mass (M) of fucoidans represents an obstacle to their medical application. We therefore investigated two series of degraded fucoidan fractions with regard to their CXCL12 binding and inhibition of CXCL12-induced effects in Raji cells. In addition, semisynthetic β-1,3-glucan sulfates were examined to get more information about the impact of M and degree of sulfation (DS). Degradation of the fucoidans from Saccharina latissima (S.l.-SP; 481-77.0 kDa) and Fucus vesiculosus (F.v.-SP; 38.2-20.6 kDa) did not affect the respective binding capacity to CXCL12. Both the M independence and the DS dependence were confirmed by the β-1,3-glucan sulfates having significantly higher affinity to CXCL12. The chemokine binding resulted in reduced CXCL12-induced Erk1/2 signaling and chemotaxis of Raji cells which was also independent of the M. Solely the oxidatively degraded fucoidan fraction displayed a significantly reduced chemotaxis inhibition. In conclusion, degradation of fucoidans to obtain biopharmaceutically more favorable M is possible without impairing their activities targeting CXCL12. Moreover, the β-1,3-glucan sulfates should also be considered as promising candidates for further development.