Open Access Open Badges Research article

Small lytic peptides escape the inhibitory effect of heparan sulfate on the surface of cancer cells

Bodil Fadnes1*, Lars Uhlin-Hansen12, Inger Lindin13 and Øystein Rekdal13

Author Affiliations

1 Institute of Medical Biology, Faculty of Health Sciences, University of Tromsø, Norway

2 Department of Pathology, University Hospital of North Norway, Tromsø, Norway

3 Lytix Biopharma, Tromsø Science Park, N-9294, Tromsø, Norway

For all author emails, please log on.

BMC Cancer 2011, 11:116  doi:10.1186/1471-2407-11-116

Published: 31 March 2011



Several naturally occurring cationic antimicrobial peptides (CAPs), including bovine lactoferricin (LfcinB), display promising anticancer activities. These peptides are unaffected by multidrug resistance mechanisms and have been shown to induce a protective immune response against solid tumors, thus making them interesting candidates for developing novel lead structures for anticancer treatment. Recently, we showed that the anticancer activity by LfcinB was inhibited by the presence of heparan sulfate (HS) on the surface of tumor cells. Based on extensive structure-activity relationship studies performed on LfcinB, shorter and more potent peptides have been constructed. In the present study, we have investigated the anticancer activity of three chemically modified 9-mer peptides and the influence of HS and chondroitin sulfate (CS) on their cytotoxic activity.


Various cell lines and red blood cells were used to investigate the anticancer activity and selectivity of the peptides. The cytotoxic effect of the peptides against the different cell lines was measured by use of a colorimetric MTT viability assay. The influence of HS and CS on their cytotoxic activity was evaluated by using HS/CS expressing and HS/CS deficient cell lines. The ability of soluble HS and CS to inhibit the cytotoxic activity of the peptides and the peptides' affinity for HS and CS were also investigated.


The 9-mer peptides displayed selective anticancer activity. Cells expressing HS/CS were equally or more susceptible to the peptides than cells not expressing HS/CS. The peptides displayed a higher affinity for HS compared to CS, and exogenously added HS inhibited the cytotoxic effect of the peptides.


In contrast to the previously reported inhibitory effect of HS on LfcinB, the present study shows that the cytotoxic activity of small lytic peptides was increased or not affected by cell surface HS.