Sulfated galactofucan from brown alga Saccharina latissima interferes with the SDF-1/CXCR4 axis in Burkitt lymphoma cells

Fucoidans from brown algae exhibit numerous biological effects relevant for anti-tumor activity. Currently, the SDF1(CXCL12)/CXCR4 axis is considered a promising target for tumor therapy, since recent results showed that this chemokine/receptor axis plays a central role in tumor progression, angiogenesis, metastasis and therapy resistance [1]. The aim of this study was to characterize the fucoidan from Saccharina latissima and to investigate whether it influences the SDF1/CXCR4 axis. Extraction of S. latissima from Faeroe Islands provided > 5% alginic acid-free sulfated glycans, which were purified and separated into two distinct fractions by anion exchange chromatography. The more active one was identified as a sulfated branched galactofucan (SGF) with a degree of sulfation of 0.8. SGF exhibited no cytotoxic activity, but showed a variety of effects relevant for antimetastatic and antiangiogenic activity such as inhibition of heparanase, elastase and chemotaxis of tumor cells in migration and scratch assays. Investigations by flow cytometry, Western blotting, ELISA and fluorescence microscopy revealed that SGF interferes with the SDF1/CXCR4 axis in Raji cells (Burkitt lymphoma) by inhibiting the SDF1induced CXCR4 activation. Compared to fucoidan from Sigma and heparin, it was much more active. In contrast to the CXCR4 receptor antagonist AMD3100, SGF antagonizes the chemokine. In gene expression analysis, SGF additionally reduced the expression of SDF1 and several further genes important for tumor progression and metastasis. In conclusion, SGF from S. latissima was obtained in reproducible quality by an optimized isolation method. The pharmacological profile of SGF indicates potent anti-tumor effects. Based on our results, SGF should now be examined in vivo.

Acknowledgements: This study is part of the project “Algae against cancer”, financially supported by the Federal Ministry of Research and Education (BMBF).

Keywords: Brown alga, Saccharina latissima, sulfated galactofucan, Burkitt lymphoma cells, anti-tumor activity, chemokine, SDF-1(CXCL12), CXCR4

References:

[1] Cojoc M, Peitzsch C, Trautmann F, Polishchuk L, Telegeev GD, Dubrovska A. Emerging targets in cancer management: Role of the CXCL12/CXCR4 axis. Onco Targets Ther 2013; 6: 1347 – 1361.