Combined Effect of Doxorubicin with MODEL26 peptide

In 1994, six anti-microbial peptides, named Gaegurins (GGNs), were isolated from the skin of a Korean frog, Rana rugosa. GGN5, a 24-residue antimicrobial peptide, is the shortest of the six GGNs. We searched the shortest GGN5 analogue peptide with favorable bioactivity by systematic peptide modifications of both length and sequence. In the present study, we demonstrate the anticancer activity of MODEL26 peptide and investigate the combined effect of MODEL26 peptide when it is administered with doxorubicin. We also determined solution structures of MODEL26 peptide by NMR analysis.

To analyzed the anticancer activity of MODEL26 peptide, we used in vitro cytotoxicity assay. Cytotoxicity was assessed using (3-[4,5-dimethylthiazol-2-yl-5]-[3-carboxymethoxyphenyl]-2- [4-sulfophenyl]-2H tetrazolium) (MTS) colorimetric assay. To analyze the combined effect of MODEL26 peptide when administered in combination with doxorubicin, we used combination index method. The results of cytotoxicity test of MODEL26 peptide showed that it is more effective than the native peptide, GGN5, in spite of the small size. The combined effect of MODEL26 peptide and doxorubicin was at least additive and even synergistic for some combinations.

Our results suggest that the MODEL26 peptide is worthy of therapeutic development as a new anticancer agent and combination therapy with MODEL26 peptide may enhance the response rate and significantly reduce side effects by permitting a dose reduction.

References: 1. Park, J. M. et al. (1994) Biochem. Biophys. Res. Commun. 205: 948–954