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

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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.

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Acknowledgements

We thank Institute for Cancer Research, Medicine Faculty, Christian Albrecht University of Kiel, Germany for providing all the necessary facilities to execute the experiments. We also thank Department of Medical Oncology, Fudan University, Shanghai, China and College of Medicine, Shaqra University, Saudi Arabia for providing all the necessary facilities for the preparation of this manuscript. This article does not contain any studies with human patient’s participants or in vivo experiments in animals performed by any of the authors.

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  1. Khalid Rashid

    Present address: Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China

Authors and Affiliations

  1. Institute for Experimental Cancer Research, Medicine Faculty, Christian Albrecht University, Kiel, Germany

    Khalid Rashid

  2. Department of Medical Biochemistry, College of Medicine, Shaqra University, Shaqra, 11961, Saudi Arabia

    Aqeel Ahmad

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  1. Khalid Rashid
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  2. Aqeel Ahmad
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Correspondence to Aqeel Ahmad.

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Rashid, K., Ahmad, A. In Vitro Selective Suppression of Tumor Cells by an Oncolytic Peptide in Pancreatic Ductal Adenocarcinoma. Int J Pept Res Ther 27, 863–873 (2021). https://doi.org/10.1007/s10989-020-10131-6

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