Cytotoxic Effect of Synthetic Peptides on Normal and Cancerous Cells

Abstract

This research explores anti‐cancer activities of synthetic peptides that inhibit the CMG helicase, the major DNA replicative helicase. Targeting CMG helicases for cancer treatment provides a unique opportunity to develop a cancer treatment that effectively eradicates cancer cells without affecting normal healthy tissues. This approach exploits a natural difference between activation of CMG helicases in normal and cancer cells. Collective evidence shows that normal cells – compare to cancer cells – possess higher levels of CMG helicase reserves available for activation throughout the S phase. Cancer cells, on the other hand, activate the majority of their helicases at once, thereby exhausting their helicase reserves. Based on this, we hypothesized that our peptides – by targeting the CMG helicase – would lead to the death of cancer cells, while spare corresponding normal cells.In this study, we utilized two types of cancerous and normal cell lines: pancreatic cancerous Hs766T and normal hTERT‐HPNE cell lines, as well as glioma M059J and normal glial SVGp12 cell lines. Cells were plated in 96 well plates at a density of 3,000 cells/well and treated with different concentrations of studied peptides. Viabilities of cells were scored by a colorimetric CCK‐8 assay. According to our IC50 calculations, both cancerous cell lines were much more sensitive to the peptide treatments compare to their normal counterparts. Indeed, we observed that normal cell lines required almost 25 times higher concentrations of peptides to reach the same cytotoxic effect as the cancerous cells. Interestingly, we contrast these results with our studies with Gemcitabine, a therapeutic agent that is currently used for cancer treatment. Unlike our studied peptides, treatments with Gemcitabine led to an equal demise of both cancerous and normal cells.