In Vitro Selective Suppression of Tumor Cells by an Oncolytic Peptide in Pancreatic Ductal Adenocarcinoma
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In Vitro Selective Suppression of Tumor Cells by an Oncolytic Peptide in Pancreatic Ductal Adenocarcinoma Khalid Rashid1,2 · Aqeel Ahmad3 Accepted: 22 October 2020 © Springer Nature B.V. 2020
Abstract 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. Keywords Anticancer peptide · Peptide design · PDAC · Proliferation · Necrosis · MPSC · KOR-19
Introduction Pancreatic ductal adenocarcinoma (PDAC) is without doubt by far the utmost dangerous menace and a potential source of death all through the world and it is a significant general wellbeing trouble both in the established and emerging nations (Negi et al. 2017; Neoptolemos et al. 2001). Almost all kinds of cancerous cells share numerous attributes, for example, empowering replicative everlasting status, avoiding cell fatality, and getting away from the host immune system (Wu et al. 2014). Malignant tumor growth can be * Aqeel Ahmad [email protected] 1
Institute for Experimental Cancer Research, Medicine Faculty, Christian Albrecht University, Kiel, Germany
2
Present Address: Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
3
Department of Medical Biochemistry, College of Medicine, Shaqra University, Shaqra 11961, Saudi Arabia
effectively treated by surgery or potential radio- or chemotherapy remains the standard treatment of the decision for the various types of advanced cancer including PDAC (Arruebo et al. 2011).
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