In Vitro Selective Suppression of Tumor Cells by an Oncolytic Peptide in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a typically violent sort of malignancy and a major source of morbidity and mortality worldwide. Most of the radiation as well as chemotherapeutic agents used for the treatment of PDAC exhibit strong adverse effects with low specificity. Henceforth, a need for an alternative demanded that prompted us to design a novel anticancer peptide (KOR-19) in such a way that it interacts predominantly with cancer cells but exhibits low toxicity with normal mammalian cells. Cell proliferation (XTT) assay and crystal violet assay revealed that the novel designed peptide exhibited vital toxic activities against four different PDAC cell lines (BxPC3, Colo-357, Panc89, and Panc1). On the opposite, this peptide depicted negligible or very low toxicity towards a non-cancerous primary mouse pancreatic stellate cells (MPSC). In the LDH-release assay, we have detected potential membrane damaging properties of KOR-19 as its major mode of action. Further, the hemolytic assay revealed very low or negligible toxic activities towards both mouse- and human RBCs. The flow cytometric analysis demonstrated that the KOR-19 expanded both apoptotic and necrotic cell death in all PDAC cell lines in a dose-dependent manner. Morphological assessments also supported the notion of necrosis assassination of cancer cells as there were elevated swollen vesicle-like structure and cell aggregation noticed in a cell type-dependent manner. In summary, KOR-19 exhibits excellent "druggable" properties due to its promising oncolytic and growth inhibitory activities against PDAC cells, making it a promising agent for the future remedy choice for PDAC.