%0 Journal Article
%T Small lytic peptides escape the inhibitory effect of heparan sulfate on the surface of cancer cells
%A Bodil Fadnes
%A Lars Uhlin-Hansen
%A Inger Lindin
%A £¿ystein Rekdal
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-116
%X 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.A subgroup of cationic antimicrobial peptides (CAPs) constitutes a promising group of novel anticancer agents with a new and unique mode of action and a broad spectrum of anticancer activity. CAPs induce cell death by increasing the membrane permeability of the target cells and are therefore unaffected by multidrug resistance mechanisms seen with conventional chemotherapeutic drugs [1-5]. Moreover, several CAPs display a higher specificity for cancer cells versus normal cells in comparison to conventional chemotherapy [6,7]. Their potential as anticancer agents has been further established by in vivo studies, as these peptides have been shown to induce regression of primary tumors [8,9] and prevent metastases [10-13]. Recently we reported that intratumoral injection of a short CAP, LTX-302, derived from the naturally occurring CAP bovine lactoferricin (LfcinB), leads to a local inflammation followed by a complete regression of the tumor. Interestingly, local tre
%U http://www.biomedcentral.com/1471-2407/11/116