In Vitro Characterization of Novel Protegrin-1 Analogues Against Neoplastic Cells

Even with the great advances in cancer therapies, cancer remains the major cause of death worldwide. The use of high doses of anti-cancer chemotherapeutic drugs eventually causes the inevitable damage in non-neoplastic cells. New, selective, and more effective drugs are therefore urgently required to fight cancer. In this study, the anticancer activity of new peptide analogues (P1 and P2) derived from natural peptide, protegrin-1 (PG-1) were evaluated against human breast carcinoma cell lines (MCF-7) and human non-neoplastic mammary epithelial cell lines (MCF-10A), human hepatocellular carcinoma cells (HepG2) and Vero cells. The CC₅₀ values of cancer cells were significantly lower (P < 0.01) compared to non-neo-plastic cells after treating with P1 and P2 analogues. The analogues of PG-1 showed lower percentage of Lactate Dehydrogenase release (P < 0.001) from non-neoplastic cells compared to cancer cells and low haemolytic potential (P < 0.001) compared to PG-1. The P1 and P2 analogues were shown to be able to induce cancer cell senescence and apoptosis in a p53-dependent pathway which in turn, induced caspase activities and subsequent cell death. Overall, these results suggested that designing shorter peptides, as well as altering the number and position of positive charged residues in P1 and P2 analogues resulted in reduction of their toxicity to non-neoplastic cells and increased selectivity towards cancer cells. Increased selectivity also suggests its potential use to be developed as delivery vectors in the design of chemotherapeutic anticancer drugs.