Expression of a novel peptide derived from PCNA damages DNA and reverses cisplatin resistance.

Abstract

An 8 amino acid peptide sequence derived from proliferating cell nuclear antigen (PCNA) has been shown to effectively kill several breast cancer and neuroblastoma cell lines when added exogenously to cell cultures. In this study, the expression of the 8 amino acid peptide sequence (caPeptide) was placed under control of a tetracycline responsive promoter in MDA-MB-231 cells. Endogenous expression of the peptide resulted in an increase in genomic DNA damage. CaPeptide induction combined with treatment of sublethal doses of cisplatin resulted in a marked increase in death of the cisplatin-resistant MDA-MB-231 cell line. CaPeptide was found to interact with POLD3, one of the subunits of DNA polymerase delta necessary for binding to PCNA. These results suggest an important line of inquiry into the possible role that caPeptide might play in the reversal of cisplatin resistance in breast and other cancers. This is of particular interest in those cancers where cisplatin is the first line of chemotherapy and where the acquisition of resistance is a common malady.